Brick Pollitt (Paul Newman), a former high school football star, spends a drunken night jumping hurdles on the school athletic field in a tragic attempt to recapture his glory days. He falls and injures his right leg.
Brick and his older brother, Gooper (Jack Carson), visit the family plantation in Alabama to celebrate their father's 65th birthday. The family rumor is that the wealthy patriarch "Big Daddy" Pollitt (Burl Ives) may have contracted colon cancer and would be forced to quickly settle his will, leaving his money and land to one of his two sons before he dies by the end of that year.
Gooper and his pregnant wife Mae (Madeleine Sherwood) have gone to great lengths to stay in Big Daddy's good favor (including having numerous children to carry on the Pollitt name... all of whom Gooper and Mae ignore or mistreat), hoping to eventually secure the plantation for themselves. Brick's strong-willed wife Maggie (Elizabeth Taylor) is clever and outspoken, and holds no small amount of contempt for Gooper and Mae's entitled attitudes and obnoxious offspring. Brick, now on crutches, drinks heavily and argues with Maggie about the dismal state of their marriage: Maggie still adores Brick, though she is troubled by his self-destructive behavior, and Brick is angry and sullen towards Maggie because of a yet unspecified incident involving his deceased friend, Skipper. Adding to the pressure is Gooper and Mae's constant criticism of Brick and Maggie due to Brick's alcoholism and the fact that they are childless.
Big Daddy and his wife Ida (Judith Anderson) arrive home from the Mayo Clinic where Big Daddy received the news that he is not dying of cancer after all. They are greeted at the airport by Gooper, Mae, and their annoying brood of five unruly kids, but Big Daddy ignores them and is driven home by Maggie, whom he truly cares for. Brick refuses to greet his father or come down for the party, and remains in his room, drinking.
The family doctor (Larry Gates) who had previously examined Big Daddy speaks privately with Gooper and Brick, confessing that he lied to the family about Big Daddy's condition to preserve their happiness. In reality, Big Daddy has terminal colon cancer and will soon be dead within a few months. The brothers initially keep the information to themselves, but Brick soon tells Maggie, who is deeply saddened.
As the evening wears on, Big Daddy grows annoyed with the party and his sycophantic family and ventures upstairs to speak with Brick, his favorite son. He chastises him for his excessive drinking, and for his cold treatment of Maggie. Brick grows defensive and even violent when Big Daddy brings up the subject of Skipper, Brick's old football buddy who had leapt from a hotel window to his death. Realizing that there is more to the story, Big Daddy brings Maggie into the conversation. She explains that she hated Brick's football career because he always put it before her, and that she hated Skipper for distracting Brick from his marriage (Note: it is implied that Brick and Skipper may have had a homosexual relationship which may explain Brick's lack of intemacy with the opposite sex as well as his alcoholism). Maggie describes a drunken episode between herself and Skipper in which she considered seducing him simply to spite her husband, but reconsidered at the last minute. The says that Skipper refused to respond to her advances (implying, but not fully explaining, that Skipper was homosexual too). Skipper later called Brick, seeming to think that he and Maggie had actually made love (though he had been too drunk to remember clearly). Skipper tearfully tried to apologize to his best friend, but Brick angrily hung up on him. Skipper killed himself soon after, and Brick blamed Maggie for the tragedy. Brick angrily leaves the house as a thunderstorm begins. Big Daddy prevents his drunken son from getting into the car and driving home, but Brick reveals to his father that the doctor had lied, and that his illness is terminal. A shocked Big Daddy goes to the basement to be alone.
During this time, Gooper and Mae had been trying to convince Big Momma to settle her Big Daddy's will. Big Momma is still unaware of her husband's condition. As the old woman begins to feel stress from all the hubub, Mae lets slip that Gooper told her that Big Daddy's cancer test was positive. The doctor has no choice but to admit the truth. Big Momma is at first overcome, but then firmly states that her husband will not be dying anytime soon, desperately trying to hold together the last traces of family unity. Maggie joins the conversation, and speaks calmly to Big Momma to soothe her, whereas Gooper and Mae continue to hound her with demands. The rivalry between Mae and Maggie becomes clear: Maggie sees Mae as a dishonest, greedy and selfish interloper who married Gooper for his parents wealth and does not care about anyone but herself; Mae (who has five children and is pregnant with a sixth), believes Maggie does not deserve any inheritance because she is childless and her husband drinks.
Meanwhile, Brick has followed his father to the cellar. Big Daddy sits in silence as the apologetic doctor explains that there is no use in hiding the truth. He gives Big Daddy morphine and a syringe for the pain, and returns upstairs. Brick and Big Daddy slowly begin to rehash the past, with Brick pointing out that Big Daddy's version of family love consists only of money and power. Big Daddy admits that he does not care for many of his famly members, including his wife, and that he built his empire so that people would know the great things he was capable of. After further prodding, Big Daddy recollects his own father: a boxcar tramp with no real job and no authority. Though he first speaks of his father with hostility, Big Daddy begins to smile as he remembers the fun he had as a child. He admits that he had loved his father more than anything, though he had been poor and overlooked by society. Brick becomes overwrought with emotion and trashes the basement, breaking the expensive items that his father had bought over the years to demonstrate his wealth. Once he calms down, he finally sees eye to eye with his father and the two weakened men help each other up the stairs.
Maggie, Gooper, Mae, and Big Momma are still in a heated conversation in the living room over Big Daddy's will with Gooper and Mae wanting the majority of his estate when he passes on. Brick overhears his brother and sister-in-law mocking him for his drinking habit, and calmly intervenes. Big Daddy speaks to his wife with newfound respect and affection, and has adopted a positive outlook despite his condition. To halt the argument about the inheritance, Maggie tells the family that she is finally pregnant. Mae is outraged and calls her a liar, but Big Daddy and Big Momma are happy at the news. Even Gooper believes "that girl's got life in her." Brick goes upstairs and calls for Maggie. In their bedroom, Maggie thanks Brick for going along with her lie: she is not really pregnant, but wanted to give Brick's parents some hope for the future. Brick assures her that they "are through with lies and liars in this house." The lock the door, rekindling their romance at last.