The Piano Lesson is set in Pittsburgh in 1936, with all the action taking place in the house of Doaker Charles. A 137-year-old, upright piano, decorated with totems in the manner of African sculpture, dominates the parlor.
The play opens at dawn. Boy Willie, Doaker's nephew, knocks at the door and enters with his partner, Lymon. Two have come from Mississippi to sell watermelons. Willie has not seen his sister Berniece, who lives with Doaker, for three years as he has been serving a sentence on the Parchman Prison Farm.
Willie asks his uncle for a celebratory drink: the Ghosts of the Yellow Dog have drowned Sutter in his own well. Willie intends to sell the family piano and use the money to buy Sutter's land, the land his ancestors once worked as slaves. Doaker, however, is sure Berniece will not part with the piano. Indeed, Avery Brown—a preacher who has been courting Berniece since her husband Crawley died—has already tried to get her to sell it. Willie schemes to get in touch with the prospective buyer himself.
Suddenly Berniece cries out off-stage, "Go on get away." Berniece claims she has seen Sutter's ghost, calling Boy Willie's name. She is convinced that her brother pushed Sutter into the well. Shaken, she refuses to cooperate with his plans.
Three days later, Doaker's brother Wining Boy, a wandering, washed-up recording star, sits at the kitchen table discussing the recent events with the men. Wining Boy mentions that he heard Willie and Lymon were on Parchman Farm. Willie explains that some whites had tried to chase Willie, Lymon, and Berniece's husband Crawley from some wood they were pilfering. Crawley fought back and was killed while the other two went to prison. The men reminisce about Parchman and sing an old work song.
Doaker then explains the piano's history to Lymon. During slavery, a man named Robert Sutter, the recently deceased-Sutter's grandfather, owned the Charles family. He wanted to make an anniversary present out of his friend's piano but could not afford it. Thus he traded a full and half grown slave—Doaker's grandmother Berniece and his father—for the instrument. Though initially Sutter's wife loved the piano, she eventually came to miss her slaves, falling desperately ill. So, Sutter asked Doaker's grandfather, Willie Boy, to carve the faces of his wife and child into the piano. Willie Boy did not only carve his immediately family, however, but included his mother, father, and various scenes from the family history.
Years after slavery, Berniece and Boy Willie's father, Boy Charles, developed an obsession over the piano, believing that as long as the Sutters held it, they held the family in bondage. Thus, on July 4, 1911, he, Doaker, and Wining Boy stole it. Later that day, lynchers set Boy Charles's house on fire. He fled to catch the Yellow Dog, but the mob stopped the train and set his boxcar on fire. Boy Charles died along with the hobos in his car, all of whom became the ghosts of the railroad.
Once Doaker has finished his story, Willie and Lymon attempt to move the piano. Berniece enters and commands Willie to stop, since the piano is their legacy. Berniece invokes the memory of their mother, who attended to the piano until the day she died. She attacks Boy Willie for perpetuating the endless theft and murder in their family, blaming him for the death of her husband. Suddenly, Maretha, Berniece's daughter, is heard screaming upstairs in terror, as Sutter's ghost has appeared again.
The following morning, Wining Boy enters with a suit he has been unable to pawn. Shrewdly, he sells his suit to Lymon, promising that it has a magical effect on the ladies. Lymon and Boy Willie plan to go out the local picture show and find some women.
Later that evening, Berniece appears preparing a tub for her bath. Avery enters and proposes to Berniece anew. Berniece refuses and wonders why everyone tells her she cannot be a woman unless she has a man. Changing the subject, Berniece asks Avery to bless the house in hopes of exorcising Sutter's ghost. Avery suggests that she use the piano to start a choir at his church. Berniece replies that she leaves the piano untouched to keep from waking its spirits.
Several hours later, Boy Willie enters the darkened house with Grace, a local girl. They begin to kiss and knock over a lamp. Berniece comes downstairs and orders them out. As Berniece is making tea, Lymon returns, looking for Willie. He is tired of one-night stands and dreams of finding the right woman. Musing on Wining Boy's magic suit, he withdraws a bottle of perfume from his pocket and gives it to Berniece and they kiss.
The final scene begins the next day with Willie telling Maretha of the Ghosts of Yellow Dog. He has already called the buyer about the piano. Berniece enters and once again orders Willie out of her house. They argue anew and Willie invokes the memory of his father, arguing that he only plans to do as he might have done. Willie and Lymon begin to move the piano. Berniece exits and reappears with Crawley's gun.
Suddenly a drunken Wining Boy enters, comically breaking the tension of the scene. He sits down to play a song he wrote in memory of his wife, shielding the piano from Willie. A knock at the door follows, and Grace enters. She and Lymon have a date for the picture show and suddenly Sutter's presence asserts itself. Grace flees with Lymon, leaving only the members of the Charles family and Avery in the house.
Avery moves to bless the piano. Boy Willie intercedes, taunting Sutter as Avery attempts his exorcism. He charges up the stairs, and an unseen force drives him back. He charges back up, and then engages with Sutter in a life-and-death struggle. Suddenly, Berniece realizes what she must do and begins to play the piano. "I want you to help me," she sings, naming her ancestors. A calm comes over the house. Willie reappears and asks Wining Boy is he is ready to catch the train back south. Willie says goodbye to his sister, and Berniece gives thanks.