The protagonist is Bill Masen, a biologist who has made his living working with triffids—tall, venomous, carnivorous plants capable of locomotion. Due to his background, Masen suspects they were bioengineered in the U.S.S.R. 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 from a stinger. 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 satellite weapons, triggered accidentally). After unbandaging his eyes he finds the hospital in chaos, with staff and patients all unsighted. He wanders through an anarchic London full of blind inhabitants and slowly becomes enamoured of wealthy novelist Josella Playton, who he rescues when he discovers her being forcibly used as a guide by a blind man. Intrigued by a single light on top of Senate House in an otherwise darkened London, Bill and Josella discover a group of sighted survivors led by a man named Beadley, who plans to establish a colony in the countryside. They decide to join the group.

The polygamy implicit in Beadley's scheme appalls some group members, 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. They are each 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.

Soon Masen's followers begin to fall sick and die of an unknown disease. When he wakes one morning to find the survivors have left him, he returns to the University Tower in an attempt to find Josella, but his only lead is an address left behind by Beadley's group. Joined by a repentant Coker, Masen drives to the address, a country estate called Tynsham in Wiltshire. He finds part of the Beadley group, now led by Miss Durrant, who eventually tells him that Beadley went to Beaminster a few days before he arrived. There has been no sign of Josella so far.

Masen and Coker decide to follow Beadley to Dorset. They find various small groups of blind and sighted people along the way, but without finding the slightest trace of Beadley. Eventually they decide to separate, Coker returning to help at Tynsham, while Masen heads for the Sussex Downs after remembering a remark Josella made about friends she had there.

En route, Masen rescues a young sighted girl named Susan, who he finds trapped alone at home, while her young brother lies dead in the garden, killed by a triffid. He buries the boy and takes Susan with him. A few days later, during a night of heavy rain, they see a faint light in the distance. Upon reaching it, they finally discover Josella and her friends.

They attempt to establish a self-sufficient colony in Sussex with some success, but they are constantly under threat from the triffids which mass around the fenced exterior. Several years pass, until one day a representative of Beadley's faction lands a helicopter in their yard and reports that his group has established a colony on the Isle of Wight. Durrant's talk of Beaminster was a deliberate attempt to throw Masen off the scent. Whilst they are reluctant to leave their own settlement, the group decide to see the summer out in Sussex before relocating to the Isle of Wight.

However, their plans are accelerated by the arrival of the militaristic representatives of a new despotic and self-appointed government, who arrive in a heavily-armoured car. Masen recognises the leader as a ruthless young man he encountered on a scavenging expedition in London, who he watched cold-bloodedly execute one of his own party who had fallen ill.

After feigning agreement with the latter's plans, which include taking Susan as hostage while Masen is given a large number of blind people to use on the farm as slave labour, Masen's group throw a party, during which they encourage the visitors to get drunk.

Creeping out of the house whilst the visitors are fast asleep, they disable the armoured car by pouring honey into the fuel tank and drive through the gates, leaving them open for the triffids to pour in.

The novel ends with Masen's group having reached the Isle of Wight, determined to one day destroy the triffids and reclaim their world.