In 1912 New Orleans, a seamstress named Eudora is reading the story of The Frog Prince to her daughter, Tiana, and her friend, Charlotte La Bouff. Charlotte finds the story to be romantic, while Tiana proclaims she will never kiss a frog. The years pass, and by 1926 Tiana has grown into an aspiring young chef who works two jobs, both as a diner waitress, so she can save enough money to start her own restaurant, a dream she shared with her late father James.
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 Charlotte is the perfect candidate. Eli “Big Daddy” La Bouff, a rich sugar baron and Charlotte’s father, is hosting a masquerade ball in Naveen’s honor. Charlotte hires Tiana to make beignets for the ball, giving her enough money to buy an old sugar mill to convert into her restaurant.
Meanwhile, Naveen and his valet Lawrence run into Dr. Facilier, a voodoo witch doctor. Inviting them into his emporium, Facilier convinces the pair that he can make their dreams come true. However, neither man gets what they are 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, Tiana discovers she may lose the mill to a higher bidder. Tiana then meets Naveen, who, believing her to be a princess because of her costume, asks her to kiss him and break Facilier’s curse. Tiana reluctantly agrees, in exchange for the money needed to outbid the other buyer. However, instead of Naveen turning back into a human, Tiana is turned into a frog herself. A chase ensues, and Tiana and Naveen narrowly escape to a bayou.
At the bayou, Tiana and Naveen meet Louis, a trumpet-playing alligator who longs to be human, and Ray, a Cajun firefly naively in love with the Evening Star, which he thinks is another firefly called Evangeline. Louis and Ray offer to lead Tiana and Naveen to the good voodoo priestess Mama Odie, who they believe 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.
When the four find Mama Odie, she tells them that Naveen must kiss a true princess in order to break the spell. They return to New Orleans to find Charlotte, who is the princess of the Mardi Gras Parade, but only until midnight. 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 captured by the demons and brought to Facilier.
After Ray tells Tiana that Naveen truly loves her, Tiana goes to the Mardi Gras parade only to find a human “Naveen” marrying Charlotte; but Ray rescues the real Naveen and steals the charm that disguises Lawrence. Ray finds Tiana, gives her the charm and attempts to hold off the demons so she can escape, but Facilier mortally wounds him by stepping on him. Facilier then finds Tiana and offers to make her restaurant dream come true in exchange for the charm. Realizing she would rather be with Naveen, Tiana snatches the charm from Facilier and destroys it. The angered voodoo spirits claim Facilier himself as payment for his debts and drag him into their world forever.
Tiana and Naveen reveal their love to each other and explain the situation to Charlotte, who agrees to kiss Naveen. However, the clock strikes midnight right before she can kiss him, but the two decide they are content to live together as frogs. Then Ray dies from his wounds, but at the funeral another evening star appears, revealing that Ray is finally with Evangeline, who turns out to be a firefly after all. Tiana and Naveen are wed by Mama Odie. Because of Tiana’s new status as princess, they are restored back to human form after their kiss. The couple return to New Orleans to celebrate, and Tiana and Naveen finally buy and open the new restaurant.