Twyla and Roberta first meet within the confines of a state home for children, St. Bonny's (named after St. Bonaventure), because each has been taken away from her mother. Roberta's mother is sick; Twyla's mother "just likes to dance all night." We learn immediately that the girls look different from one another: one is black, one is white, although we aren't told which is which. Despite their initially hostile feelings, they are drawn together because of their similar circumstances.
The two girls turn out to be, in famous phrase, "more alike than unalike." They were both "dumped" there. They become allies against the "big girls on the second floor" (whom they call "gar-girls," a name they get from mishearing the word "gargoyle"), as well as against the home's "real orphans," the children whose parents have died. They share a fascination with Maggie, the old, sandy-colored woman "with legs like parentheses" who works in the home's kitchen and who can't speak.
Twyla and Roberta are reminded of their differences on the Sunday that each of their mothers comes to visit and attend church with them. Twyla's mother Mary is dressed inappropriately; Roberta's mother, wearing an enormous cross on her even more enormous chest. Mary offers her hand, but Roberta's mother refuses to shake Mary's hand and Mary begins cursing. Twyla experiences twin humiliations: her mother's inappropriate behavior shames her, and she feels slighted by Roberta's mother's refusal.
Twyla and Roberta meet again eight years later during the 1960s, when Twyla is "working behind the counter at the Howard Johnson's on the Thruway" and Roberta is sitting in a booth with, "two guys smothered in head and facial hair." Roberta and her friends are on their way to the west coast to keep an appointment with Jimi Hendrix. The episode is brief but long enough for the two to show resentment towards each other's ways of life.
The third time Twyla and Roberta meet is 20 years after they first met at St. Bonnys. They are both married and meet while shopping at the Food Emporium, a new gourmet grocery store. Twyla describes the encounter as a complete opposite of their last. They get along well and share memories of the past. Roberta is rich and Twyla is lower middle class. Twyla is married to a firefighter; Roberta is married to an IBM executive.
The next time the two women meet, "racial strife" threatens Twyla's town of Newburgh, NY in the form of busing. As she drives by the school, Twyla sees Roberta there, picketing the forced integration. Twyla is briefly threatened by the other protesters; Roberta doesn't come to her aid. Roberta's parting remark unsettles Twyla:
"Maybe I am different now, Twyla. But you're not. You're the same little state kid who kicked a poor old black lady when she was down on the ground. You kicked a black lady and you have the nerve to call me a bigot."
Twyla replies, "Maggie wasn't black." Either she does not remember that she was black, or she had never classified her sandy skin as black. Twyla decides to join the counter-picketing across the street from Roberta, where she spends a few days hoisting signs that respond directly to Roberta's sign.
We meet Twyla and Roberta once more; this time it is in a coffee shop on Christmas Eve, years later, probably in the early 1980s. Roberta wants to discuss what she last said about Maggie. The conversation is sympathetic but ends on an unresolved note.