The protagonist is Bill Masen, a biologist who has made his living working with triffids – tall, venomous carnivorous plants capable of locomotion and communication, whose extracts are superior to fish or vegetable oils. Due to his background, Masen suspects that they were bioengineered in the USSR and accidentally released into the wild. The result is worldwide cultivation of triffids. The narrative begins with Bill Masen in hospital, his eyes bandaged after having been splashed with triffid poison. During his convalescence he is told of an unexpected green meteor shower. The next morning, he learns that the light from the unusual display has rendered any who watched it completely blind (later in the book, Masen speculates that the "meteor shower" may have been orbiting weapons, triggered accidentally). After unbandaging his eyes, he wanders through an anarchic London full of blind inhabitants; and later becomes enamored of wealthy novelist Josella Playton, forcibly used as a guide by a blind man. Intrigued by a single light on top of Senate House in an otherwise darkened city, Bill and Josella discover a group of sighted survivors led by a man named Beadley, who plans to establish a colony in the countryside, and decide to join the group.
The polygamy implicit in Beadley's scheme appalls some of the group, especially the religious Miss Durrant; but before this schism can be dealt with, a man called Wilfred Coker stages a fire at the university and kidnaps a number of sighted individuals, including Bill and Josella, each of whom is chained to a blind person and assigned to lead a squadron of the blind, collecting food and other supplies, while beset by escaped triffids and rival scavengers. When Masen's followers are dying of an unknown disease, he attempts to find Josella, but his only lead is an address left behind by Beadley's group. Joined by a repentant Coker, he drives to the place, a country estate called Tynsham in Wiltshire, but finds neither Beadley nor Josella. After some days, Masen finds Josella at her friends' country home in Sussex, while Coker returns to Tynsham and later rejoins Beadley. En route, Masen is joined by a young sighted girl named Susan. Among other refugees, including some blind, they attempt to establish a self-sufficient colony in Sussex, menaced chiefly by triffids. Years pass until a helicopter pilot representative of Beadley's faction reports that his group has established a colony on the Isle of Wight. Masen and his followers are reluctant to leave their own colony, but are provoked to do so by soldiers of a despotic new government. After feigning agreement with the latter's plans, the Masens disable the soldiers' vehicle and flee to the Isle of Wight, determined to destroy the triffids and reclaim Earth.