Mark Corley, a Los Angeles police detective, helps his estranged son, Trent, out of jail just as an alien invasion begins. The entire population of the city is sucked into various spaceships by a blue light. Mark leads a group of surviving humans through underground subway tunnels to escape, though most of the humans are killed or abducted one by one. The survivors – Mark, Trent, transit operator Audrey, and a homeless man known only as "Sarge", who is immune to the blue light due to his blindness – escape to the marina following its nuclear destruction, only to be abducted into the alien flagship by a towering alien tanker.
On board the spaceship, Mark tries to find his son and storms his way into various chambers, where he meets up with survivor Elaine and her transformed boyfriend Jarrod (from the first film). Elaine explains that Jarrod retained control of his mind despite being transformed into a bio-mechanical alien soldier. Though Elaine is three months pregnant, her pregnancy has accelerated and she gives birth to a newborn daughter. Elaine dies during the delivery, and Mark and Jarrod team up to destroy the alien ship by setting alien explosives inside the ship's control systems. As Jarrod fights various alien warriors, Mark rescues Audrey but is too late to save his son. Trent has his brain taken and placed in another alien bio-mechanical machine creature. Sarge sacrifices himself so that Mark, Audrey and the baby can escape from the chamber. Jarrod is killed when he fights the alien leader but destroys the ship, which crashes in rural Laos.
As the alien spaceship repairs itself, Mark, Audrey and the baby are found by a pair of human siblings, outlaw Sua and his sister Kanya, who are evading both aliens and local militia. As they trek through the jungle, the group discovers that the human baby grows at an accelerated rate from a newborn into a three-year-old in just one day. Sua and Kanya lead Mark, Audrey and the baby to a hidden human resistance hideout located in local ruins. There, Harper, a medical officer and former drug smuggler, examines the baby girl and learns about her unique DNA. Harper believes her blood may be the key to defeating the aliens due to her evolving DNA. Using the child's blood and recovered alien technology, Harper develops a serum he believes will free the bio-mechanical soldiers from alien control and restore their human personality. Though Sua insists on killing all the bio-mechanical soldiers, Mark convinces Sua to allow him to save Trent.
While on a patrol, Kanya encounters a four-legged tanker alien and sacrifices herself by luring it into an old minefield left over from the Vietnam war. Though she destroys it, she unwittingly gives away their location to the alien ships searching for the human newborn child. They converge on the human base. During the resulting battle, several members of the human resistance, including Harper, are killed. Mark enters a grounded alien ship, where he uses Harper's serum to turn the mind-controlling blue light into a red light that frees the mind-controlled bio-mechanical soldiers. Before he can deploy it, the alien leader and his horde of alien warriors attacks the human resistance and disables the light. Trent, his mind restored after encountering his father, fights back inside a giant alien tanker. While the alien leader is busy fighting Trent, the child fixes and deploys the red light, freeing the bio-mechanical soldiers, and Trent defeats the alien leader. With Earth saved, Audrey names the girl Rose after Mark's deceased wife.
Ten years later, Rose, now a fully-grown adult, has taken control of an alien ship, and Trent is her second-in-command. Rose leads freed bio-mechanical soldiers and humans in an assault on the other alien ships around the Moon, including the mothership.