Robert Morgan (Vincent Price
) is the last man on earth, as far as he can tell. A plague killed everyone else on the planet several years ago. He was immune to it, and can only guess why. Vampires that were formerly human attack Morgan's home every night
Morgan's days are spent shoring up his home against the vampire hordes, picking up supplies in the abandoned city, and eliminating his enemies by searching out and destroying the bloodsuckers while they sleep. He maintains mirrors and garlic strands around his house and fashions stakes on his lathe to use on the walking dead. He also conducts experiments on the bacteria that caused this plague in an effort to find a cure.
He remembers the early days of the plague, when his former friend and lab partner, Ben Cortman (Giacomo Rossi Stuart
) tried to warn Morgan of what was to come. Morgan dismissed his fears and continued life as usual.
The vampires outside Morgan's home are led by Ben Cortman, who has made it his personal mission to kill Morgan. "Morgan, come out!" is the nightly chant that torments him.
He remembers the disease blanketing the earth. His daughter Kathy (Christi Courtland
) fell ill and went blind. His wife Virg (Emma Danieli
) was horrified and wanted to get help, but any reported case of plague would result in immediate government pickup, death and cremation of the body. Before leaving for work, Morgan ordered Virg not to call anyone, but, tormented by the little girl's cries, she did. As Morgan arrived home, he saw the government truck leaving. Kathy was gone.
His solitary existence is painful. He gets on the radio every day, calling out on different frequencies, trying to find another human still alive. In his tortured dreams, he remembers when his wife returned from the dead to seek his blood, after she succumbed to the plague. Because he couldn't bear to throw her body in the cremation pit where others were taken, he buried her himself--and when she came back from the dead as a vampire, he had to drive a stake through her heart.
One day, to his amazement, he finds a dog. He is so excited to have a companion that he overlooks several signs that all is not right with the animal. Eventually, he realizes that the dog is also infected and that he must kill it.
While burying the dog, Morgan encounters Ruth Collins (Franca Bettoia
), a woman walking through the park in the sunshine! Even though he's suspicious of her story of how she survived, he takes her home with him. She reacts violently to a garland of garlic cloves he brings out, but she claims that she's always had a weak stomach. Morgan catches her injecting herself with something, and she's forced to admit that she too is infected but that she and others like her have developed a serum that lets them control the disease. By regular injections, they keep the disease in check: they are able to live in the daylight and do not turn to vampirism. Ruth also warns Morgan that her people are coming for him because, in his zeal to kill vampires, he has been killing people like her who have the disease under control. Morgan injects Ruth with some of his own blood and cures her of the disease completely. His blood is the permanent cure that Ruth and others like her have been searching to find.
At this moment, however, the soldiers come for him. Before Ruth can tell them that Morgan has found a cure, he is surrounded and shot. As he stumbles to his death, he tells the crowds that they are freaks and that he is "the last man on earth"!