Houston, April 1947. "Mama" Carrie Watts has lived with her son Ludie and his disagreeable wife Jessie Mae in a small apartment for 15 years. One night they all have trouble sleeping. Jessie Mae nags at Mama persistently, and Mama begs Ludie to let her return home to Bountiful.
The next day, Mama takes her latest pension check, packs a bag, and goes to both the train and bus station; at both places, dispatchers tell her that no trips go to Bountiful anymore. She buys a bus ticket for a nearby town and heads off with great excitement, evading Ludie and Jessie Mae.
Along the way, she meets a young woman named Thelma, who is sad that her husband is away in the military. Mama complains about Jessie Mae, wishing she still had her own house. Mama abruptly tells Thelma that she did not love her own husband, but rather was always in love with another man; she cries in explaining that she could not marry him because their fathers disliked each other.
When Mama makes it to her stop with Thelma, she is shocked to learn that the friend she wanted to see in Bountiful died just days earlier, and that the town itself no longer has any residents. She also realizes that she left her purse on the bus, but the dispatcher calls ahead to have it brought back. Mama blithely wonders with Thelma why her life is filled with trouble yet relief.
Thelma takes off to her destination, and Mama lies down to sleep on a bench. Hours later, the town sheriff comes by to tell the dispatcher he'd gotten a call looking for Mrs. Watts. When the sheriff tells her that Ludie is coming to pick her up in the morning, Mama begs to be allowed to see Bountiful, only 12 miles away. She breaks down in tears, explaining that she just wants to see her old home once before she dies. The sheriff calls a doctor to have her sedated.
At dawn, with Mama in a much calmer mood, the sheriff agrees to drive Mama to Bountiful. She is dismayed as they drive through the abandoned town, with its handful of buildings overgrown with weeds. He drives her out to her old house, also long since empty, and they chat. Mama eventually becomes emotional, knowing that she has outlived her family and her house.
The sheriff leaves Mama alone to walk through the house for a while. Ludie drives to the house and finds her sitting on the porch. She says she got her wish. Ludie regrets not bringing her earlier, saying, "I just thought it'd be easier if we never saw the house again," and he refuses to go in.
As they stand outside, Ludie gets upset recalling Mama's father's funeral at the house when he was 10, pointing out that he's never had children, feeling that he's never done good by his mother or wife. He confesses that he's been repressing the memories of his childhood, because they do not help him.
Mama wonders what will still be left after they and the house are gone: the river, the fields, the trees, the smell. She tells Ludie they are all part of the land that keeps changing.
Jessie Mae shows up and confronts Ludie to tell Mama the new "rules" she has for her, such as no more running away. Mama agrees, saying that her trip has been "more than enough to keep me happy for the rest of my life." Ludie suggests that they should all get along better, and gets mad at Jessie Mae for distrusting his mother.
Mama takes a last moment to sit on the ground and look at the house, saying goodbye. She quietly cries as Ludie drives them away.