Donna Trenton (Dee Wallace-Stone) is a frustrated suburban housewife whose life is in turmoil after her husband learns about her having an affair. Brett Camber (Billy Jacoby) is a young boy and a son of a mechanic (Ed Lauter) whose only companion is a St. Bernard named "Cujo." Cujo is bitten by a bat with rabies and his behavior begins to change. When Donna and her young son, Tad (Danny Pintauro), drive out to the home where Cujo and his owners live, the gentle Cujo has been driven insane by rabies and has killed one of his owners. Worse, their car gives out near the mechanic's house, and Donna and Tad are trapped inside while the massive dog waits outside, attacking repeatedly.
Eventually Donna makes an attempt to dash for the house but is attacked by Cujo, the only safety being the car. Cujo brutally kills anyone and everyone who comes to the house, including the local Sheriff. After a brutal struggle between the desperate mother and the relentless animal, Donna takes advantage of a momentary distraction and beats Cujo with a baseball bat and then stabs him with the handle when the bat breaks. As Donna attempts to revive her son, who has passed out due to the extreme heat, Cujo tears through the kitchen window and launches himself at the two. Donna kills Cujo with the dead Sheriff's revolver, manages barely to resuscitate Tad, and is joined by her husband outside who has just arrived as the carnage ends