Astor was born Nancy Witcher Langhorne in Danville, Virginia, in the United States. Her father was Chiswell Dabney Langhorne and her mother was Nancy Witcher Keene. Her father's earlier business venture had depended at least in part upon slave labour, and the outcome of the American Civil War caused the family to live in near-poverty for several years before Nancy was born. After her birth her father began working to regain the family wealth, first with a job as an auctioneer and later with a job that he obtained with the railroad by using old contacts from his work as a contractor. By the time she was thirteen years old, the Langhornes were again a rich family with a sizable home. Chiswell Langhorne later moved the family to their estate, known as Mirador, in Albemarle County, Virginia.

Nancy Langhorne had four sisters and three brothers. All of the sisters were known for their beauty; her sister Irene later married the artist Charles Dana Gibson and became a model for the Gibson girl. Nancy and Irene both went to a finishing school in New York City. There Nancy met her first husband, Robert Gould Shaw II, a cousin of the Colonel Robert Gould Shaw, who commanded the all-black 54th Massachusetts Volunteer Infantry Regiment. They were married in New York City on October 27, 1897, when she was 18.

The marriage was a disaster. Shaw's friends accused Nancy of becoming puritanical and rigid after she married, while her friends claimed that Shaw was an alcoholic rapist. They remained married for four years and had one son, Bobbie. Nancy left Shaw numerous times during their marriage, the first during their honeymoon. In 1903, Nancy's mother died and the now divorced Nancy moved back to Mirador to try to run the household, but was unsuccessful. She left on a tour of England and fell in love with the country. Since she had been so happy there, her father suggested that she move to England. Nancy was reluctant, so he told her the move had been her mother’s wish and would also be good for Nancy's younger sister, Phyllis. Nancy and Phyllis finally moved to England in 1905.
England

The earlier trip to England had launched Nancy's reputation there as an interesting and witty American. Her tendency to be witty and saucy in conversation, yet religiously devout and almost prudish in behavior, confused many of the English men but pleased some of the older socialites. They liked conversing with the lively and exciting American who at the same time largely conformed to decency and restraint. Nancy also began at this time to show her skill at winning over critics. She was once asked by an English woman, "Have you come to get our husbands?" Her unexpected response, "If you knew the trouble I had getting rid of mine..." charmed her listeners and displayed the wit that later became famous.

Despite her denial, however, she indeed married an Englishman. Her second husband, Waldorf Astor, was born in the United States but his father had moved the family to England when Waldorf was twelve and raised his children as English aristocrats. The couple were well matched from the start. Not only were they both American expatriates with similar temperaments, but they were of the same age, being born on the same day, 19 May 1879. He shared some of Nancy's moral attitudes, and his heart condition may have encouraged him toward a restraint that she found comforting. The marriage's success, therefore, seemed assured.

After the Astors married, Nancy moved into Cliveden, a lavish estate in Buckinghamshire on the River Thames that was a wedding gift from Astor's father, and began her life as a prominent hostess for the social elite. The Astors also owned a grand London house, No. 4 St. James's Square, which is now the premises of the Naval & Military Club. A blue plaque unveiled in 1987 commemorates Astor at St. James's Square. Through her many social connections, Lady Astor became involved in a kind of political circle called Milner's Kindergarten. Considered liberal in their age, the group advocated unity and equality among English-speaking people and a continuance or expansion of British imperialism.

The political significance of Milner's Kindergarten was limited, but it yielded a much more significant result for Lady Astor personally. It was the source of her friendship with Philip Kerr, which was to be one of the most important relationships of her life. Indeed, it came at a critical juncture for both of them. The two met shortly after Kerr had suffered a spiritual crisis regarding his once devout Catholicism. The two of them were both searching for spiritual stability and their search led them toward Christian Science, to which they both eventually converted. Astor's beliefs and activities as a Christian Scientist would become one of the most consistent elements of her life.

Philip Kerr's conversion came only after experimenting with Eastern religion, but he later became a spiritual advisor for Astor. In time, his bitter rejection of Catholicism also influenced Lady Astor, intensifying her own anti-Catholicism. She was also affected when her friendship with Hillaire Belloc, who was Catholic, began to grow cold because of his disdain for the rich and her efforts to convert his daughters to Christian Science. The loss of that relationship further alienated her against Roman Catholicism. Lady Astor's devotion to Christian Science was more intense than orthodox, and she sent some practitioners away for disagreeing with her. But she was deeply committed to her own interpretation of the faith and held to it almost fanatically. Many of her letters from that time on mentioned Christian Science, and letters from others to her joked about her efforts to convert peers to her beliefs. This vehemence of belief demonstrates that she was, by this time, considered "insane" by secular intellectuals; it is therefore by all accounts astonishing that she was taken even remotely seriously in later years by the English establishment.

During World War I Cliveden was a hospital for Canadian soldiers. Although Astor, as a Christian Scientist, did not believe in the use of medical practices, she got along well with the doctors, especially Colonel Mewburn, a surgeon. She justified her position there by helping those who needed non-medical assistance. Lady Astor became known as a friend to soldiers, and that proved useful when she ran for office. At the same time, the horrors of poison gas attacks and the deaths of friends turned her against war itself.

Several elements of Lady Astor's life to this point influenced her first campaign, but the main reason she became a candidate in the first place was her husband's situation. He had enjoyed a promising career for several years before World War I in the House of Commons, but then he succeeded to his father's peerage as the 2nd Viscount Astor. This meant that he automatically became a member of the House of Lords and forfeited his seat of Plymouth Sutton in the House of Commons. So Lady Astor decided to contest the vacant Parliamentary seat.

Astor had several disadvantages in her campaign. One of them was her lack of connection with the women's suffrage movement. The first woman elected to the British Parliament, Constance Markievicz, said Lady Astor was "of the upper classes, out of touch". Countess Markievicz had been in Holloway prison for Sinn Féin activities during her election, and other suffragettes had been imprisoned for arson; Astor had no such background. Even more damaging to Astor's campaign were her well-known hostility to alcohol consumption and her ignorance of current political issues. These points did not endear her to the people of Plymouth, the constituency from which she was elected. Perhaps worst of all, her tendency to say odd or outlandish things sometimes made her look rather unstable.

However, Astor also had some positive attributes in her campaign, such as her earlier work with the Canadian soldiers, her other charitable work during the war, her vast financial resources for the campaign and, most of all, her ability to improvise. Her ability to turn the tables on the hecklers was particularly useful. Once a man asked her what the Astors had done for him and she responded with, "Why, Charlie, you know," and later had a picture taken with him. This informal style baffled yet amused the British public. She rallied the supporters of the current government, was pragmatic enough to moderate her Prohibitionist views, and used women’s meetings to gain the support of female voters. A By-election was held on 28 November 1919, and she took up her seat in the House on 1 December as a Tory Member of Parliament.

Astor's Parliamentary career was the most public phase of her life, making her an object of both love and hatred. Her presence almost immediately gained attention, both as a woman and as someone who did not follow the rules. On her first day in the House of Commons, she was called to order for chatting with a fellow House member, not realising that she was the person who was causing the commotion. She did try in some ways to minimise disruption by dressing more sedately than usual and by avoiding the bars and smoking rooms frequented by the men.

Early in her first term, a fellow Member of Parliament named Horatio Bottomley, who felt Astor was an obstacle in his desire to dominate the "soldier’s friend" issue, sought to ruin her political career. He did this by capitalising on the first substantial controversies in which she participated, namely her opposition to divorce reform and her efforts to maintain wartime alcohol restrictions. He depicted her as a hypocrite in his newspaper, saying that the Divorce Reform Bill she opposed allowed women to have the kind of divorce she had had in America. However, a budget crisis and his bitter tone caused this effort to backfire. Bottomley eventually went to prison for fraud, a fact that Astor used to her advantage in later campaigns.

Among Astor's early political friends were the first female candidates to follow her to Parliament, including members of the other parties. The first of these friendships began when Margaret Wintringham was elected after Astor had been in office for two years, but the most surprising might have been her friendship with "Red Ellen" Wilkinson, a former Communist representative in the Labour Party. Astor later proposed creating a "Women’s Party", but the female Labour MPs thought it was a ridiculous idea because at that time their party had power and promised them positions. Astor conceded this, but her closeness with other female MPs dissipated with time and by 1931 she became hostile to female Labour members such as Susan Lawrence.

Lady Astor's accomplishments in the House of Commons were relatively minor. She never held a position with much influence. Indeed, the Duchess of Atholl (elected to Parliament in 1923, four years after Lady Astor) rose to higher levels in the Tory Party before Astor did, and this was largely as Astor wished. She felt that if she had a position in the party, she would be less free to criticise her party’s government. One of her few significant achievements in the House was the passage of a bill she sponsored to increase the legal drinking age to eighteen unless the minor has parental approval.

During this period Lady Astor did some significant work outside the political sphere. The most famous was her support for nursery schools. Her involvement with this cause was somewhat surprising because she was introduced to it by a socialist named Margaret McMillan who believed that her dead sister still had a role in guiding her. Lady Astor was initially sceptical, but later the two women became close and Astor used her wealth to aid their social efforts.

Although she was active in charitable efforts, Astor also became noted for a streak of cruelty and callousness. On hearing of the death of a political enemy, she openly expressed her pleasure. When people complained about this, she did not apologise but instead said, "I’m a Virginian; we shoot to kill". A friend from Virginia, Angus McDonnell, had angered her when he married without consulting her after having agreed to seek her permission first. She later told him, regarding his maiden speech, that he "really must do better than that". During the course of her adult life, Astor alienated many others with her sharp words as well.

The 1920s were the most positive period in Parliament for Astor as she made several effective speeches and successfully introduced the Intoxicating Liquor Bill (nicknamed ‘Lady Astor’s Bill’) raising the legal age for consuming alcohol in a public house from 14 to 18. Her wealth and persona also brought attention to women who were serving in government. Furthermore, she worked to bring more women into the civil service, the police force, education reform, and the House of Lords. She remained popular in her district and well liked in the United States during the 1920s, but this period of success is generally believed to have declined in the following decades

The 1930s were a decade of personal and professional difficulty for Lady Astor. An early sign of future problems came in 1928 when she won only a narrow victory over the Labour candidate. In 1931 her problems became more acute when Bobbie, her son from her first marriage, was arrested for homosexuality. Because Bobbie had previously shown tendencies toward alcoholism and instability, Astor's friend Philip Kerr, now Marquess of Lothian, told her that the arrest might be positive for him. This prediction would turn out to be incorrect. Astor also made a disastrous speech stating that alcohol use was the reason England's national cricket team was defeated by the Australian national cricket team. Both the English and Australian teams objected to this statement. Astor remained oblivious to her growing unpopularity almost to the end of her career.

A mixed element in these difficult years was Astor's friendship with George Bernard Shaw. He helped her through some of her problems, but also made some things worse. They held opposing political views and had very different temperaments, but he liked her as a fellow non-conformist, and she had a fondness for writers in general. Nevertheless, his tendency to make controversial statements or put her into awkward situations proved to be a drawback for her.

After Astor's son Bobbie was arrested, Gertrude Ely, a Pennsylvia Railroad heiress from Bryn Mawr, Pa offered to provide a guided tour to Moscow with Lady Astor and Shaw. Although it was helpful in some ways, this trip turned out to be bad overall for Lady Astor's political career. During the trip Shaw made many flattering statements about Stalinist Russia, while Nancy often disparaged it because she did not approve of Communism. She even asked Joseph Stalin directly why he had slaughtered so many Russians, but many of her criticisms were translated into innocuous statements instead, leading many of her conservative supporters to fear she had "gone soft" on Communism. (Her question to Stalin may have been translated correctly only because he insisted that he be told what she had actually said.)According to Miss Ely's diary, she was disappointed as only Shaw was able to meet Stalin. Furthermore, Shaw's praise of the USSR made the trip seem like a coup for Soviet propaganda and made her presence there disturbing for the Tories.

 
The period from 1937 to the end of the war was traumatic on a personal level. In the period of 1937-38 Astor's sister Phyllis and only surviving brother died. In 1940 her close friend and spiritual advisor Lord Lothian died too. Although his influence had a definite negative aspect, he had been her closest Christian Scientist friend even after her husband converted. George Bernard Shaw’s wife also died about two years later. During the war, Astor got into a fight with her husband about chocolate and soon after he had a heart attack. After this, their marriage grew cold, probably due at least in part to the harsh effects of such a petty argument and her subsequent discomfort with his health problems. She ran a hospital for Canadian soldiers as she had before, but openly expressed a preference for the veterans of the previous World War.

It was generally believed that it was Lady Astor who, during a World War II speech, first referred to the men of the 8th Army who were fighting in the Italian campaign as the "D-Day Dodgers". Her implication was that they had it easy because they were avoiding the "real war" in France and the future invasion. The Allied soldiers in Italy were so incensed that Major Hamish Henderson of the 51st Highland Division composed a bitingly sarcastic song to the tune of the haunting German song "Lili Marleen" (popularised in English by Marlene Dietrich) called "The Ballad Of The D-Day Dodgers".

Lady Astor did not feel that her final years were a period of personal decline. Instead, in her opinion, it was her party and her husband who caused her retirement in 1945. The Tories felt that she had become a liability in the final years of World War II, and her husband told her that if she ran for office again the family would not support her. She conceded, but with irritation and anger, according to contemporary reports.

Lady Astor's retirement years proved difficult, especially for her marriage. She publicly blamed her husband for forcing her to retire; for example, in a speech commemorating her 25 years in parliament she stated that her retirement was forced on her and that it should please the men of Britain. The couple began traveling separately and living apart soon after. Lord Astor also began moving toward left-wing politics in his last years, and that exacerbated their differences. However, the couple reconciled before his death on 30 September 1952.

After 1956 Lady Astor became increasingly isolated, although in 1959 she was honoured by receiving the Freedom of City of Plymouth. Her sisters had all died, "Red Ellen" Wilkinson died in 1947, George Bernard Shaw died in 1950, and she did not take well to widowhood. Her son Bobbie became increasingly combative and after her death he committed suicide. Her son Jakie married a prominent Catholic woman, which hurt his relationship with his mother, and her other children became estranged from her. Ironically, these events mellowed her and she began to accept Catholics as friends. However, she stated that her final years were lonely. Lady Astor died in 1964 at her daughter's home at Grimsthorpe Castle in Lincolnshire. She was cremated and her ashes interred at the Octagon Temple at Cliveden.
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