After the destruction of an asteroid headed for Earth, the chemical fallout causes all cold-blooded animals, such as frogs and snails, to mutate into large, aggressive monsters. During the evacuation of Fairfield, teenager Joel Dawson is separated from his girlfriend Aimee but promises to find her. He watches his parents die when their car is crushed by a monster's leg.Seven years later, Joel, now aged 24, lives in one of many underground bunkers called "colonies". The other survivors, except for him, have romantically paired up with each other while fighting monsters and scavenging for supplies. Joel is assigned to work as a cook, as he is notorious for freezing in dangerous situations. When a giant ant breaches his colony, killing one of the survivors, Joel decides he's had enough and sets off on a quest to reunite with Aimee so that he doesn't end up alone. The other survivors give him a map and a crossbow despite their fear that he will not survive.Passing through the suburbs, Joel is attacked by a giant toad-monster but is saved by a stray dog named "Boy", who follows Joel on his journey, warning him against poisonous berries and other dangers. Joel falls into a nest of worm-monsters called "Sand-Gobblers", when two survivors, Clyde Dutton and his adopted daughter Minnow, rescue him. They are heading north to the mountains, where the colder weather and higher elevation means fewer monsters. They teach Joel some basic survival skills: how to fight, sense danger, and find food. Minnow also shows Joel how not all monsters are hostile, demonstrating how "You can always tell in their eyes". The pair invite Joel to stay with them, but Joel insists that he must find Aimee. As they part ways, Clyde gifts Joel with a grenade.As Joel continues west, Boy is attacked by a giant centipede-monster. Joel freezes, but eventually shoots and kills the monster with his crossbow, saving Boy. Sheltering in an abandoned motel, they meet a damaged robot named Mav1s. Before her battery dies, Mav1s powers Joel's radio long enough to briefly contact Aimee, where he learns that new survivors have reached her colony, promising to lead them away to safety. The next day, Joel and Boy are attacked by a Queen Sand-Gobbler. They hide, but Boy barks, giving away their position. Joel kills the Queen with the grenade but yells at Boy for putting them in danger, causing Boy to run away. After swimming across a river, Joel is covered in poisonous leeches and starts to hallucinate from their venom. He swallows some leaves as an antidote before he is rescued.Joel wakes to finally see Aimee. She leads a beach colony of elderly survivors, who all depend on her. Joel is introduced to the new survivors, led by Cap, a former Royal Australian Navy sailor who has managed to procure an old yacht. As everyone celebrates their imminent departure, Aimee confesses she is glad to see Joel, but has no romantic interest in him as she is still mourning the death of someone close to her. Joel decides to return to his colony and contacts them on the radio, learning that it has become unsafe and that they too must leave soon. Cap sends Joel some berries, which he recognizes as poisonous. Realizing Cap is not to be trusted, he rushes to warn Aimee but is knocked unconscious.Joel, Aimee, and the rest of her colony are tied up on the beach. Cap reveals that he and his crew are actually pirates who raid colonies for food and fuel. He summons a crab-monster rigged with a makeshift electric collar to eat the colonists, but Joel and Aimee escape their bonds. Boy returns and saves Aimee, who steals a hand cannon from one of the pirates. Joel is about to kill the crab, but he determines that the monster is not hostile by looking into its eyes, and instead uses the cannon to destroy the collar. The crab leaves Joel unharmed and sinks the yacht, devouring Cap and the pirates.Joel recommends Aimee and her colony head north. They share a romantic goodbye kiss, and Aimee promises she will find him. Joel gives her a book containing all of his survival knowledge, and treks all the way back to his colony, persuading them to head for the mountains. On the radio, Joel sends a message to other colonies, sharing his experiences so they will also be ready to leave. As everyone heads north, Clyde and Minnow, already in the mountains, wonder if Joel will survive the next journey.