Taking place concurrently with the events of Skyline, Los Angeles police detective Mark Corley rescues his estranged son, Trent, from jail just as an alien invasion begins. The city’s population is being abducted by a mysterious blue light. Mark leads a group of survivors, including Trent, transit operator Audrey, and blind homeless man “Sarge,” through subway tunnels to evade capture. Despite their efforts, most are killed or taken. The remaining group reaches the marina only to be abducted into the alien flagship after the city’s destruction by a nuclear bomb.
On the spaceship, Mark searches for his son and encounters Elaine and her transformed husband Jarrod, characters from the first film. Elaine, who is now rapidly advancing in her pregnancy, gives birth to a daughter. Elaine dies during childbirth, and Mark teams up with Jarrod to sabotage the ship. Jarrod sacrifices himself to combat the alien leader, allowing Mark to rescue Audrey. However, Trent’s brain is taken and placed into an alien bio-mechanical creature. The ship crashes in rural Laos after Jarrod’s final act of defiance.
Mark, Audrey, Sarge, and the rapidly growing baby escape the crashing spaceship. Sarge succumbs to his injuries shortly after meeting Sua and Kanya, members of a drug cartel fighting both aliens and rogue ex-policemen. As they trek through the jungle, they discover the human baby matures quickly, transforming into a three-year-old in one day. They reach a hidden human resistance base in local ruins, where they capture the rogue policeman leader, Huana.
Harper, a medical officer and former drug chemist, studies the unique DNA of the baby girl and develops a serum from her blood that he believes can free bio-mechanical soldiers from alien control. Kanya sacrifices herself by luring an alien into a minefield, but this gives away their location to alien ships. During the battle that follows, many resistance members, including Harper, are killed. Mark infiltrates an alien ship, attempting to convert the mind-controlling blue light into a red light that frees the soldiers, but is thwarted by an alien attack.
In the climactic battle, Trent regains his mind and joins the fight against the aliens. With the child’s help, Trent repairs the cannon that releases the red light, freeing the bio-mechanical soldiers. The alien leader is defeated, and Audrey names the girl Rose after Mark’s deceased wife. Earth is saved, and the bio-mechanical soldiers are freed from alien control.
Ten years later, Rose, now a fully-grown adult, commands an alien ship with Trent as her second-in-command. She leads an assault on remaining alien ships around the Moon, including the mothership, with a mix of freed bio-mechanical soldiers and humans.