The protagonist is Bill Masen, an Englishman who has made his living working with "Triffids," plants capable of aggressive and seemingly intelligent behaviour: they are able to move about on their three "legs", appear to communicate with each other and possess a deadly whip-like poisonous sting that enables them to kill and feed on the rotting carcasses of their victims. The book implies they were bioengineered in the Soviet Union and then accidentally released into the wild when a plane carrying their seeds was shot down. Triffids begin sprouting all over the world, and their extracts prove to be superior to existing vegetable oils. The result is worldwide cultivation of Triffids.

The narrative begins with Masen in hospital, his eyes bandaged after having been splashed with droplets of triffid venom in a lab accident. During his convalescence he is told of the unexpected and beautiful green meteor shower that the entire world is watching. He awakes the next morning to a silent hospital and learns that the light from the unusual display has rendered any who watched it completely blind. After unbandaging his eyes, he wanders through a largely sightless London, watching civilization collapsing around him. Masen meets a sighted woman, novelist Josella Playton. She and Masen begin to fall in love and decide to leave London.

After being lured by a single light in an otherwise darkened city, Bill and Josella discover and join a group of sighted survivors at a London university led by a man named Beadley, who are planning to establish a colony in the countryside. Beadley wishes to take only sighted men who will take several wives to rapidly rebuild the human population. The polygamous principles of this scheme appall one of the other leaders of the group, the religious Miss Durrant. Before this schism can be dealt with a man called Wilfred Coker takes it upon himself to save as many of the blind as possible. He stages a mock fire at the university and during the ensuing chaos kidnaps a number of sighted individuals including Bill and Josella. Each is chained to a squad of blind people and forced to lead them around London, collecting rapidly diminishing food and supplies. Bill and his group finds themselves beset by escaped triffids and an aggressive rival gang of scavengers led by a ruthless red-haired man.

Masen nevertheless sticks with his group until the people in his charge all begin dying of some unknown disease. He leaves and attempts to find Josella, but his only lead is an address left behind by the now-departed members of Beadley's group. Thrown together with a repentant Coker, he drives to the place, a country estate named Tynsham in Wiltshire, but neither Beadley nor Josella are there; Durrant has taken charge and organised the community along "Christian" lines. Masen and Coker fruitlessly search for Beadley and Josella for several days, before Bill remembers a chance comment Josella made about a country home in Sussex. He sets off in search of it, while Coker returns to Tynsham.

Bill is joined by a young sighted girl named Susan; they succeed in locating Josella, who is indeed at the Sussex house. Bill and Josella consider themselves to be married, and see Susan as their daughter. They attempt to make the Sussex farm into a self-sufficient colony, but with only marginal success, as the triffids grow ever more numerous, crowding in and surrounding their small island of civilization. Years pass, during which it becomes steadily harder to keep out the encroaching plants.

One day a helicopter pilot representative of Beadley's faction lands at the farm and reports that the group has established a successful colony on the Isle of Wight, and that Coker survived to join them. Despite their ongoing struggles, the Masens are reluctant to leave their home, but their hand is forced by the arrival the next day of a squad of soldiers who represent a despotic new government which is setting up feudal enclaves across the country. Masen recognizes the leader, Torrence, as the redheaded man from London. Torrence announces his intention to place many more blind survivors under the Masens' care and to move Susan to another enclave. After feigning general agreement, the Masens disable the soldiers' vehicle and flee during the night. They join the Isle of Wight colony, and settle down to the long struggle ahead, determined to find a way to destroy the triffids and reclaim Earth for humanity.