On a single summer evening, the Pollitt family gathers to celebrate the birthday of patriarch Big Daddy.
On the previous evening, Big Daddy's son Brick broke his leg while trying to jump hurdles at the school track. His wife Margaret chides him for his foolish behavior and his constant state of drunkenness, but mostly she is trying to impress – and seduce – her husband. Brick has refused to sleep with Maggie ever since his friend Skipper died. Maggie desperately wants Brick to sleep with her – both to satisfy her own physical needs, and because she wants to get pregnant.
Maggie feels a particularly urgent need to have a baby because she needs to produce an heir. Big Daddy is dying, although he has not been told this yet, and he does not have a will. Maggie is terribly afraid of being poor, so she wants to make sure that she and Brick have a secure place in Big Daddy's will. In order to do so, however, she must contend with Brick's brother Gooper and his wife's significant brood of children.
Brick, for his part, is too numb with liquor to care much about anything. He makes clear that he is disgusted by Maggie and completely uninterested in anything she has to say. The only thing that rises him to emotion is the topic of Skipper. He and Brick were best friends, but Maggie thinks their relationship was a bit more than that. She called Skipper out on his attraction to her husband, and to prove her wrong Skipper slept with her. Both Maggie and Skipper, however, were making love to one another in lieu of Brick. Shortly thereafter, Skipper began to self-destruct, and soon died. This is the point at which Brick turned to liquor as well.
They are interrupted by the arrival of more family members. Everyone but Big Daddy and Big Mama knows that Big Daddy is dying, but he and his wife were told by the doctor that he just had a spastic colon. Tonight, the sons will tell their mother the truth.
After a round of happy birthday, the older couple is left alone. Big Daddy is cruel to Big Mama, who insists that she loves him even though he doesn't believe her. He is frustrated that she has taken charge of the estate since he became sick, but now that he knows that his days are no longer numbered (he thinks) he is going to take it all back and return Big Mama to her place.
Big Mama leaves and Big Daddy summons Brick. Big Daddy tries to open up to Brick, but his son isn't interested in talking. The older man persists in making an effort at communication, telling stories about his travels in Europe and how horrible poverty is. He worked hard to get where he is now, financially, and now that he is free of cancer, he is going to enjoy his wealth properly. Big Daddy speaks of taking on a mistress – Big Mama never interested him.
Brick, however, does interest him. He tries to coerce his son into admitting why he drinks, eventually stealing his crutch and knocking him to the ground. With some effort, Big Daddy zeros in on the truth – that it all comes back to Skipper. The night that Skipper and Maggie slept together, Skipper called Brick and tried to make an admission. Brick hung up on him, because he was entirely incapable of even allowing the possibility of homosexuality into his outlook. It is this disgust with himself and with his world that drove Brick to the bottle.
In his fury about being confronted with the truth of his relationship with Skipper, Brick tells Big Daddy that he has cancer.
Big Daddy leaves, upset, and the rest of the family enters. With difficulty, Big Mama is told that Big Daddy has cancer, although she refuses to believe it at first. She tells Maggie that Brick has to get his act together, so that he can take care of the estate when Big Daddy is gone.
Mae and Gooper pounce on this, and they produce legal papers that would establish a will favorable to their interests. They try to convince Big Mama that this arrangement is for the best, due to Brick's alcoholism and Maggie's childlessness. Maggie takes this as her cue and announces grandly that she is with child. Her brother- and sister-in-law don't believe her for a second, but Big Mama rejoices in the good news, and leaves to tell Big Daddy.
Maggie and Brick are left alone. He says she was very bold to make that lie, but Maggie intends to turn the lie into truth. She takes away Brick's liquor, and says that she will not get him any more drinks until he consents to sleep with her. Big Mama runs in, searching for the morphine that the doctor left for Big Daddy – the pain has set in. She leaves, and as the play ends, Maggie tells Brick that she loves him as Brick wonders "wouldn't it be funny if that were true?"