Act One: "Fun and Games"
George and Martha engage in dangerous emotional games. George is an associate professor of history and Martha is the daughter of the president of the college. After they return home, Martha reveals she has invited a young married couple, whom she met at the party, for a drink. The guests arrive – Nick, a biology professor (who Martha thinks teaches math), and his wife, Honey. As the four drink, Martha and George engage in scathing verbal abuse in front of Nick and Honey. The younger couple is first embarrassed and later enmeshed. They stay.
Martha taunts George aggressively, and he retaliates with his usual passive aggression. Martha tells an embarrassing story about how she humiliated him with a sucker-punch in front of her father. During the telling, George appears with a gun and fires at Martha, but an umbrella pops out. After this scare, Martha's taunts continue, and George reacts violently by breaking a bottle. Nick and Honey become increasingly unsettled and, at the end of the act, Honey runs to the bathroom to vomit, because she had had too much to drink.
Act Two: "Walpurgisnacht"
Traditionally, "Walpurgisnacht" is the name of an annual witches' meeting (satiric in the context of the play). Nick and George are sitting outside. As they talk about their wives, Nick says that his wife had a "hysterical pregnancy". George tells Nick about a time that he went to a gin-mill with some boarding school classmates, one of whom had accidentally killed his mother by shooting her. This friend was laughed at for ordering "bergin". The following summer, the friend accidentally killed his father while driving, was committed to an asylum, and never spoke again. George and Nick discuss the possibility of having children and eventually argue and insult each other. After they rejoin the women in the house, Martha and Nick dance suggestively. Martha also reveals the truth about George's creative writing escapades: he had tried to publish a novel about a boy who accidentally killed both of his parents, but Martha's father would not let it be published. George responds by attacking Martha, but Nick separates them.
George suggests a new game called "Get the Guests". George insults and mocks Honey with an extemporaneous tale of "the Mousie" who "tooted brandy immodestly and spent half her time in the upchuck". Honey realizes that the story is about her and her "hysterical pregnancy". The implication is that she trapped Nick into marrying her because of a false pregnancy. She feels sick and runs to the bathroom again.
At the end of this scene, Martha starts to act seductively towards Nick in George's presence. George pretends to react calmly, reading a book. As Martha and Nick walk upstairs, George throws his book against the door. In all productions until 2005, Honey returns, wondering who rang the doorbell (Martha and Nick had knocked into some bells). George comes up with a plan to tell Martha that their son has died, and the act ends with George eagerly preparing to tell her. In what is labeled the "Definitive Edition" of the script, however, the second act ends before Honey arrives.
Act Three: "The Exorcism"
Martha appears alone in the living room, shouting at the others to come out from hiding. Nick joins her. The doorbell rings: it is George, with a bunch of snapdragons in his hand, calling out, "Flores para los muertos" (flowers for the dead), a reference to the play and movie A Streetcar Named Desire, also about a marriage and outside influences. Martha and George argue about whether the moon is up or down: George insists it is up, while Martha says she saw no moon from the bedroom. This leads to a discussion in which Martha and George insult Nick in tandem, an argument revealing that Nick was too drunk to have sex with Martha upstairs.
George asks Nick to bring Honey back for the final game – "Bringing Up Baby". George and Martha have a son, about whom George has repeatedly told Martha to keep quiet. George talks about Martha's overbearing attitude toward their son. He then prompts her for her "recitation", in which they describe, in a bizarre duet, their son's upbringing. Martha describes their son's beauty and talents and then accuses George of ruining his life. As this segment progresses, George recites sections of the Libera me (part of the Requiem Mass, the Latin mass for the dead).
At the end of the play, George informs Martha that a messenger from Western Union arrived at the door earlier with a telegram saying their son was "killed late in the afternoon...on a country road, with his learner's permit in his pocket" and that he "swerved, to avoid a porcupine". The description matches that of the boy in the gin-mill story told earlier. Martha screams, "You can't do that!" and collapses.
It becomes clear to the guests that George and Martha's son is a fiction. George has decided to "kill" him because Martha broke their rule of never speaking of him to others. Nick and Honey leave, realizing that the cause of their hosts' shameless antics was their inability to conceive. The play ends with George singing, "Who's afraid of Virginia Woolf?" to Martha, whereupon she replies, "I am, George...I am."