An alien ship arrives and hovers over Earth. After several days of silence, the ship sends out an electromagnetic pulse (EMP) that causes all electrical power and engines to fail. Over half a million people die in accidents resulting from the EMP.
The second wave of destruction is just that, a wave. The aliens set off a massive earthquake, which causes tsunamis to take out close to 3 billion people. After that, they release a virus that kills 97% of the remaining humans.
Cassie, her father and her younger brother, Sammy, survive the first three waves. They find a refugee camp in the woods made up of other survivors, but after several weeks, alien drones spot them. A few days later, what appear to be human soldiers find the camp. They fill a school bus with refugee children under the age of 12. Sammy goes with them but makes Cassie promise to take care of his stuffed teddy bear until they are reunited.
After the buses leave, the soldiers shoot the remaining refuges, except for Cassie, who manages to escape. Her father dies before a massive bomb turns what was their camp into an ash heap.
For the next five months, Cassie lives alone in the woods, foraging for food at a nearby convenience store. She figures out that the fourth wave of the invasion is what she calls Silencers. They are humans, or human-looking aliens, that stalk and kill survivors. One of them shoots her in the knee, but she is able to escape and find cover. She knows she will die if she does not get help. She also knows the Silencer who shot her is waiting to kill her if she leaves her place of cover.
Elsewhere, the object of Cassie’s infatuation before the alien invasion, a boy named Ben Parish, is struggling to survive. He caught the virus and drifts in and out of hallucinations. He remembers promising his parents that he would take care of his younger sister. Thugs attack him and his sister. They drag Ben away and start to beat him. He escapes them by running away, but he is unable to find his sister. He carries her locket as a reminder of his failure.
Ben is taken to an Air Force base and given medicine to recover. Soldiers tell him that the aliens have invaded some humans, but that the base is safe. He is shown a machine, which helps soldiers detect who is an alien. They have captured one of Ben’s friends, a person who helped him while he was sick. They point the machine at him, and it registers the person as an alien. Ben is given the opportunity to push the button to kill him, which he does.
Ben sinks into depression until a soldier named Vosch tells Ben that he can train to become a soldier, who is trained to fight aliens and help retake Earth. The training is brutal. All the recruits are given nicknames. Ben is called Zombie. He becomes his squad’s leader when he defends a new recruit, named Nugget, from the abuse of their commanding officer. Nugget is Cassie’s little brother, and he becomes devoted to Ben.
Cassie decides she would rather die trying to find her brother than bleed or freeze to death. She taunts the Silencer to kill her but ends up passing out before he does. When she wakes up, she finds herself in a bed. Her wound has been cleaned and bandaged, and she has been bathed. A young man named Evan explains that he found her and brought her home. Evan takes care of her during her recuperation, and despite her best efforts, Cassie finds herself falling in love with him. Eventually, she begins to suspect that he may actually be an alien. He insists he accompany her to try and rescue Sammy.
Ben and his team are the first to graduate from the program and be sent out on a mission to kill aliens. Nugget is too young, however, and must stay behind. Ben promises he will return for him. As the team is dropped into a city, they use their new scanners to track aliens. The scanners light up green when aliens are present. The team, which now includes a girl named Ringer, kills three aliens before an alien sniper pins them down.
As they try to make it to their rendezvous, one of their teammates is killed and another is severely wounded. Ben and Ringer try to find the sniper, but their scanners do not pick up any more aliens. Ringer tells Ben she does not believe their superiors. She thinks the people running the base are aliens and that they are using the children to kill the remaining humans. Humans killing humans could be the fifth wave.
As proof, she has Ben dig out the tracking device with which all the children have been implanted. As soon as it is removed, the scanner says she is an alien. Ben and Ringer stalk the sniper and discover it is their drill sergeant. Ben’s squad was among the first to be sent out. The aliens want to make sure the children back at the base believe that aliens are still out there and dangerous. That is why they planned to kill this first group. Instead of that plan working, the kids kill their drill sergeant. Ben insists he must return to get Nugget before he can permanently leave the base.
Soldiers in the woods attack Cassie and Evan as they near the Air Force base. Evan easily kills them. Cassie knows he is a Silencer. He is the one who shot her. He admits it, but explains that it was never his wish to kill humans. His species exist as pure energy; they have no form.
Many have been living within their human hosts for years without anyone knowing it. They are not parasites. They become the human they inhabit, sharing all their emotions and experiences. Evan is among a small group of dissenters that didn’t want to annihilate the human race, but coexist with them. The more aggressive aliens won that argument.
Evan asks her permission to join with her consciousness for a moment. Cassie opens herself up to let Evan’s energy enter her mind and is convinced of his purity and love for her. Then he pulls away so his energy will leave her. As they near the base, she convinces Evan that although it is foolhardy, she alone must enter the base if they have any hope of rescuing her brother.
Ben has Ringer shoot him in the side so he can con the aliens into allowing him back into the complex. Once inside, he intends to rescue Nugget, not realizing that Cassie is on the same mission. As the two teenagers incapacitate several humans and human/aliens, an alarm is sounded. Someone else is also within the base, wreaking havoc.
Cassie and Ben get to her brother at the same time. Together they try and escape the complex but are captured. The human/aliens take her brother away, but prepare to kill Cassie and Ben. Evan rescues all of them. He guides Cassie, Ben and Sammy to freedom, but he returns to the complex to set off a bomb to destroy it. Cassie knows there is little hope he will survive the explosion.
The aliens send out drones to find and kill those who escaped, but Ben’s squad members rescue them. As a new day dawns, it is indicated that something is making the drones fall from the sky. Ben, Cassie and Sammy watch the sunrise together.