In 1912 New Orleans, a woman is reading the story "The Frog Prince" to her daughter, Tiana, and her daughter's friend, Charlotte La Bouff. Charlotte finds the story romantic, while Tiana proclaims she would never kiss a frog. The years pass and by 1926, Tiana has become a beautiful young woman who works two jobs so she can save money to start her own restaurant, fulfilling her late father's dream.
Elsewhere, Prince Naveen of Maldonia arrives in New Orleans determined to better his financial situation. After being cut off by his parents, Naveen is forced to marry a rich southern belle. It soon becomes obvious that Tiana's best friend and the rich sugar baron's daughter, Charlotte La Bouff, is the perfect candidate. Eli "Big Daddy" La Bouff (John Goodman), Charlotte's father, is hosting a masquerade ball in Naveen's honor. Charlotte hires Tiana to make beignets for the ball, giving her just the right amount of cash needed to finally buy an old sugar mill that she wants to convert into her restaurant.
Meanwhile, Naveen and his valet, Lawrence, run into the shady Dr. Facilier, a voodoo doctor. Inviting them into his emporium, Facilier convinces the pair he can make their dreams come true. However, neither man gets what he's expecting; Naveen becomes a frog, while Lawrence is given a voodoo charm that makes him look like Naveen. Facilier intends for Lawrence to marry Charlotte, after which he will kill Big Daddy La Bouff and claim his fortune.
At the ball, Charlotte flirts with "Naveen" as Tiana learns she may lose the mill to a higher bidder. Adding insult to injury, her costume is accidentally ruined. Charlotte gives Tiana a princess costume and a tiara so she can rejoin the ball. After Charlotte returns to the party, Tiana makes a wish on the Evening Star, only to find a frog sitting next to her. The frog is Naveen, who asks Tiana (believing that she is a real princess) to kiss him and break Facilier's curse. Tiana agrees, in exchange for the money needed to outbid the other buyer. However, instead of Naveen turning into a human, Tiana is turned into a frog herself.
The pair narrowly escape to a bayou, where they encounter Louis, a trumpet-playing alligator who longs to be human, and Ray, a Cajun firefly who longs for a sparkling light he calls Evangeline. They offer to lead them to the good voodoo priestess Mama Odie, who can undo the curse. Along the way, Tiana and Naveen begin to develop feelings for each other. Meanwhile, Facilier makes a deal with the voodoo spirits, offering them the souls of the people of New Orleans in exchange for finding Naveen. Mama Odie tells the frogs that Naveen must kiss a princess in order for them to become human. Tiana and her friends return to New Orleans to find Charlotte, the princess of the Mardi Gras Parade. Naveen tells Ray he loves Tiana and is willing to give up his dreams for her, but before he can tell her directly, he is kidnapped by the demons and brought back to Facilier.
After Ray tells Tiana that Naveen truly loves her, Tiana goes to the Mardi Gras parade only to find "Naveen" marrying Charlotte. Feeling betrayed,Tiana escapes to a graveyard to be alone, while Ray and Louis are able to rescue the real Naveen and steal the charm. Ray finds Tiana and gives her the charm and attempts to hold off the demons so she can escape, but Dr. Facilier steps on him, after swatting him with his hand. Facilier confronts Tiana and offers to make her restaurant dream come true in exchange for the charm. Realizing she would rather be with Naveen, Tiana refuses and snatches the charm from Facilier and destroys it. The angered spirits claim Facilier himself as payment for his debts and drag him, as he screams for mercy, into their world forever.
Naveen is explaining the situation to a bewildered Charlotte when Tiana finds them both. Tiana reveals that she loves Naveen and would spend the rest of her days as a frog to be with him. Moved by this, Charlotte says she will kiss Naveen anyway so he and Tiana can be together. Unfortunately, Mardi Gras ends and the clock strikes midnight before she can kiss him. Louis then meets up with the frogs, holding a dying Ray in his hands. Despite what happened, Ray shows happiness for the two before he dies. A funeral is held for Ray, after which another star shines brightly next to "Evangeline."
Content to live together as frogs, Tiana and Naveen are wed by Mama Odie. As they kiss, they are turned into humans, because through their marriage, Tiana is now a princess. The two return to New Orleans where everyone celebrates the wedding and Tiana and Naveen finally buy the restaurant. "Tiana's Palace" holds a gala opening, underneath the two shining Evening Stars.