The play takes place on a New England college campus, in the home of a professor, George, and his wife, Martha, the daughter of the college president. The play begins with Martha and George returning from a party at Martha’s father’s house. They bicker drunkenly with one another, and Martha informs George that they have guests coming over, even though, as George reminds her, it is two o’clock in the morning. Martha sings, “Who’s Afraid of Virginia Woolf,” to the tune of “Who’s Afraid of the Big Bad Wolf,” which she seems to have invented at the party, and laughs hysterically at it.
The doorbell rings and George opens the door right as Martha is yelling to him “Fuck you!” Nick and Honey, their guests, look as though they regret having come. They begin to discuss the party—Nick, a new professor, expresses his gratitude for the president’s parties in helping him grow acquainted to the college. Martha and Honey excuse themselves to go to the restroom. George provokes Nick, and then tells him about the campus practice of “musical beds”—of sleeping with other professor’s wives. Nick snaps, irritated with George’s crassness.
George believes that Nick is in the Math department, but Nick explains that he teaches Biology, with a particular research focus on genetics. George accuses Nick of rearranging chromosomes in order to make everyone identical. Honey returns and tells George that she’s heard about his son—George is distressed by this news. Honey is followed into the room by Martha.
When George leaves to get more alcohol, Martha begins telling Honey and Nick about the circumstances of their marriage. She explains that she married George in part because her father had his eyes on him as a potential future president, but later lost confidence in him. George re-enters the room in the middle of her narrative. He breaks a bottle against the bar and then begins loudly singing “Who’s Afraid of Virginia Woolf.” Honey announces that she’s going to be sick.
While Martha tends to Honey, George and Nick converse: Nick tells George that Honey often gets sick, and that he married her because of a “hysterical” pregnancy. George tells Nick about a boy that he knew in high school who accidentally killed both of his parents.
Martha and Honey return and George puts on music. Martha and Nick dance close together. George introduces the next game they are going to play—entitled “Get the Guests”—and then begins to describe the plot of his second novel. The plot he describes is the story of Nick and Honey’s marriage—the false pregnancy, the wife’s mousiness. Honey runs out of the room to vomit again. When George exits to get ice, Martha seduces Nick into kissing her. When George returns, he begins to read a book and appears unfazed when Martha informs him that she is necking with one of the guests. Martha and Nick leave George, and when George hears dishes clattering in the kitchen, he throws a book at the sound, then leaves.
Martha enters the empty living room and babbles crazily to herself. Nick enters. They chat a little, and then the door chimes ring and Nick opens the door to find George. George announces that the next game they are going to play is “bringing up baby.” He begins to talk about their son, despite Martha’s pleading, and then prompts Martha to take over. She and George play off of each other, each adding details about the son’s childhood. Then George reports that while Martha was out of the room, a man from Western Union came and delivered a telegram informing them that their son had died.
When Martha asks what George did with the telegram, he says he ate it, and then laughs explosively. Nick guesses correctly that Martha and George are in fact incapable of having children. The guests say their goodbyes and leave. George puts his hand on Martha’s shoulder and begins singing, “Who’s Afraid of Virginia Woolf.” Martha answers that she is.