On Thanksgiving Day, Bart gets the entire family angry at him and runs away from home. However, when he sees what life is like on the seedy side of town (and ends up on the evening news), he realizes how good things are for him and returns home.
On Thanksgiving, Lisa is making a centerpiece for Thanksgiving which honors women such as Georgia O'Keeffe, Susan B. Anthony, and Marjory Stoneman Douglas (the latter worked her whole life to preserve the Florida Everglades). Meanwhile, Bart is in the kitchen with Marge while cooking Thanksgiving dinner, while Homer watches the Macy's Thanksgiving Day Parade and football on TV.
While Grandpa, Patty, Selma, and Jacqueline arrive and assemble at the table, Lisa brings in her carefully-crafted centerpiece and proudly presents it. Bart brings in the turkey, and he complains that the centerpiece is blocking space for the turkey. Bart and Lisa escalate into chaos, causing the centerpiece to land in the fireplace and quickly burn up, making Lisa so mad, she runs to her room in tears, and Homer and Marge send Bart to his room as punishment.
After Marge consoles Lisa, she tells Bart he can come downstairs to dinner on the condition he apologize in front of everybody. Bart scoffs at the directive and decides he doesn't have to take his punishment and decides to run away. However, Homer scolds Santa's Little Helper and confines him outside when he tries to eat some of the turkey, and Bart takes him with him.
During the walk, Bart sneaks into Burns' mansion, where he attempts to steal a freshly baked pie, but is soon caught and forced outside by the hounds. Bart and Santa's Little Helper then wander to the seedy part of town (known as "The Wrong Side of the Tracks"), and Bart donates his blood plasma at a blood bank for $12. Bart then goes to a soup kitchen, where Thanksgiving dinner is served to homeless people. There, Kent Brockman is doing a report on the dinner, where he delivers a self-serving commentary on how the patrons are forgotten on Thanksgiving. Later, Brockman interviews Bart, where he mocks his family and refuses to apologize. The family sees the report on TV, and Homer immediately calls the police.
As Bart exits the shelter, one of the bums asks Bart if he's got a home. Bart agrees, and seeing how the bums need the money more than he does, offers the money he got from his blood donation to the bums. Remorseful, Bart realizes how he has more than the bums with whom he shared Thanksgiving, decides to return home. However, once he arrives home, Bart considers what his folks might say to him. He imagines himself being greeted warmly and offering an apology, but then they scornfully mock him and laugh in his face as he grovels an apology, then begin to blame him for everything (Grandpa being old, Homer being bald, Maggie not talking, and Uncle Sam for making America lose it's spirit). Bart decides that he shouldn't have came back and goes on top of the roof.
Meanwhile, as Homer and Marge are interviewed by the police, Lisa is upstairs, writing in her diary and conceding defeat. She begins to cry due to missing Bart, after which Bart calls her outside. There, the two discuss what happened, and Bart still refuses to apologize in the belief that he has done nothing wrong. Lisa tells him to look deeper. Bart comes to realize that he hurt her feelings by destroying something that she considered dear. Bart finally apologizes and Lisa happily accepts and kisses him and a very pleased Homer watches them from the window. Finally, Homer leads the family in prayer blessing for Bart's reunion, as they enjoy an 11 p.m. Thanksgiving of leftovers and displaying the thankful spirit that was absent from the earlier debacle.