A narrator explains how humans were unaware that a race of extraterrestrials was making plans to occupy Earth. Ray Ferrier is a divorced crane operator longshoreman who works at a dock in Brooklyn, New York and lives in Bayonne, New Jersey. Ray is estranged from his children. His former wife, Mary Ann, later drops off the children, 10-year-old daughter Rachel and teenage son Robbie, at Ray's house on her way to visit her parents in Boston. Unexplained changes in the weather occur, including lightning that strikes multiple times in the middle of an intersection and disrupts all electricity.

Ray joins the crowd at the scene of the lightning strikes, and witnesses a massive "Tripod" war machine emerge from the ground and use alien weaponry to disintegrate most of the witnesses, turning them to a grey dust and leaving only their empty clothes behind. Ray collects his children, steals a car and drives to Mary Ann's home in suburban New Jersey to take refuge. The next morning, he discovers that a Boeing 747 has crashed in the street. A news team scavenging for food while surveying the wreckage explain that there are multiple Tripods that have attacked major cities including New York City, Paris, Washington, D.C., and London, and have force shields to protect them from human weapons. They also explain that the lightning was how the aliens were able to enter the Tripods. Ray decides to take the kids to Boston to be with their mother. The three are forced to abandon the stolen car after a mob takes it by force. They later survive a Tripod attack which causes a Hudson River ferry to sink. During a desperate battle between U.S. Marines and the aliens, Ray is forced to choose between being separated from Rachel and preventing Robbie from joining the fight; he lets Robbie go with the Marines, who are overwhelmed. While escaping, Ray and Rachel are offered shelter by Harlan Ogilvy, who presumes that the aliens had buried their technology on Earth millions of years ago and has delusions that they can fight against the aliens themselves by observing their operations, as they are right next to their camp.

The three remain undetected for two days, even as a probe and a group of the aliens themselves explore the basement. The next morning, Ogilvy suffers a mental breakdown while witnessing a Tripod harvesting human blood and tissue to fertilize an alien vegetation. Convinced that Ogilvy's mad shouting jeopardizes his daughter's life, Ray reluctantly kills him. The basement hideout is exposed when a second probe catches them sleeping. Rachel is soon abducted by a nearby Tripod; Ray allows himself to be abducted, and is placed in the same cage with Rachel and a number of other prisoners. As the aliens select him for harvesting, Ray takes a belt of grenades into the machine, having pulled out the pins. The Tripod is destroyed and releases the cage, with Ray and Rachel, and the other prisoners, making it out alive.

Ray and Rachel arrive in a devastated Boston, where the vegetation is dying and most of the Tripods have collapsed. Ray notices birds landing on an active Tripod, indicating that its shields are off. Ray alerts the soldiers escorting his refugee group and they shoot it down. As the soldiers advance on the downed Tripod, a hatch opens releasing a liquid; a sickly alien struggles halfway out, and then dies immediately. Ray and Rachel reach Mary Ann's parents' house, where they are reunited with Mary Ann and Robbie. The closing narration reveals that the aliens were immune to man's machines but they and their vegetation were not immune to the microbes present on Earth and that "From the moment the invaders arrived, breathed our air, ate and drank, they were doomed. They were undone, destroyed, after all of man's weapons and devices had failed, by the tiniest creatures that God in his wisdom put upon this earth. By the toll of a billion deaths, man had earned his immunity, his right to survive among this planet's infinite organisms. And that right is ours against all challenges. For neither do men live nor die in vain.".

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