Donna Trenton, portrayed by Dee Wallace, is a housewife whose world has been turned upside down after her husband, Vic, finds out about her affair. Meanwhile, young Brett Camber, son of mechanic Joe Camber, has a loyal companion in his St. Bernard named Cujo. Tragedy strikes when Cujo is bitten by a rabid bat while chasing a rabbit into a cave, leading to a severe personality change. As the dog succumbs to the illness, Brett and his mother, Mrs. Camber, set off to visit family in Connecticut, using winnings from the lottery.
However, their plans take a dark turn when Donna and her young son, Tad, set out to the Camber residence to fix their car. This is when they encounter the now-violent Cujo, who has lost all semblance of his former gentleness. The dog initially attacks their neighbor, Gary Parvier, who bravely tries to fend off the aggressive canine. Sadly, despite his efforts, Gary falls victim to Cujo's ferocity.
When Joe Camber arrives to check on Gary, he discovers the aftermath of Cujo's rampage, and before he can react further, he also becomes a target of the rabid dog. As tragedy unfolds, Donna and Tad's car faces mechanical failure, leaving them vulnerable to the stalking Cujo. They find themselves trapped, unable to escape the relentless assaults of the massive dog, all the while Vic is away on a business trip.
Vic returns home to chaos, the result of attacks by Steve Kemp, the man with whom Donna had an affair, who had vandalized their home. When he becomes aware that Donna and Tad are missing, he alerts the Sheriff, who sets out to find them. However, Donna is fighting for survival in a deadly standoff against Cujo. The unbearable heat forces her to make dire decisions, as she realizes that remaining in the car may lead to their demise from heatstroke or dehydration.
In a tense sequence, the local Sheriff arrives only to be ambushed by Cujo, leading to yet another tragic outcome as the dog prevails against him. Armed with only her courage and a determination to save her son, Donna manages a daring escape to retrieve a baseball bat when she sees Cujo distracted. After an intense confrontation, she fights back with all her strength, eventually managing to fatally wound Cujo.
Even after Cujo's initial defeat, he attempts a last-ditch attack through the kitchen window, but with the Sheriff’s revolver in hand, Donna is ready. She shoots Cujo before he can reach them. As Vic approaches the Camber home, he is filled with dread but is relieved to see Donna emerge carrying Tad, as the film builds to its gripping conclusion.
