A family in the American South is in crisis, especially the husband and wife Brick and Margaret (usually called Maggie or "Maggie the Cat"), and the crisis unspools with Brick's family over the course of one evening's gathering at the family estate in Mississippi. The party celebrates the birthday of patriarch Big Daddy Pollitt, "the Delta's biggest cotton-planter",[3] and his return from the Ochsner Clinic with what he has been told is a clean bill of health. All family members (except Big Daddy and his wife Big Mama) are aware of Big Daddy's true diagnosis: He is dying of cancer. His family has lied to Big Daddy and Big Mama to spare the aging couple pain on the patriarch's birthday, but throughout the course of the play, it becomes clear that the Pollitt family has long constructed a web of deceit for itself.

Maggie, determined and beautiful, has escaped a childhood of poverty to marry into the wealthy Pollitts, but finds herself unfulfilled. The family is aware that Brick has not slept with Maggie for a long time, which has strained their marriage. Brick, an aging football hero, infuriates her by ignoring his brother Gooper's attempts to gain control of the family fortune. Brick's indifference and his drinking have escalated with the suicide of his football buddy Skipper. Maggie fears that Brick's malaise will ensure that Gooper and his wife, Mae, inherit Big Daddy's estate.

Ben Gazzara as Brick in the original Broadway production of Cat on a Hot Tin Roof (1955)

Through the evening, each member of the family must face the issues which they have bottled up inside. Big Daddy attempts a reconciliation with the alcoholic Brick. Both Big Daddy and Maggie separately confront Brick about the true nature of his close friendship with Skipper, which appears to be the source of Brick's sorrow and the cause of his alcoholism. Brick explains to Big Daddy that the friendship troubled Maggie, who jealously believed it had a romantic undercurrent, and says Skipper took Maggie to bed to prove her wrong but could not complete the act, raising inner doubts that made him "snap." Brick also reveals that Skipper, shortly before his suicide, confessed his attraction to Brick, but Brick rejected him.

Disgusted with the family's mendacity, Brick tells Big Daddy that the report from the clinic about his condition was falsified for his sake. Big Daddy storms out of the room, leading the rest to drift inside. Maggie, Brick, Mae, Gooper, and Doc Baugh (the family's physician) decide to tell Big Mama the truth about her husband's illness, and she is devastated by the news. Gooper and Mae start to discuss the division of the Pollitt estate. Big Mama defends her husband from Gooper and Mae's proposals.

Big Daddy reappears and makes known his plans to die peacefully. Attempting to secure Brick's inheritance, Maggie tells him she is pregnant. Gooper and Mae know this is a lie, but Big Mama and Big Daddy believe that Maggie "has life." When they are alone again, Maggie locks away the liquor and promises Brick that she will "make the lie true."