It follows an Army Ranger sniper who encounters a Predator while on a mission and subsequently crosses paths with a government taskforce seeking to capture and study the creature. When it becomes clear the Predator is in fact attempting to help mankind defend itself against increasing attacks by its brethren, the sniper is forced to team up with a group of misfit military outcasts to battle the genetically modified Predator sent to Earth by its bethren to kill the fugitive.
In deep space, a spaceship is pursued and fired upon by another vessel, but escapes when it opens a wormhole. It arrives at Earth, where damage from its confrontation causes it to crash-land and a Predator known as the Fugitive ejects in a pod that comes down in Mexico, interrupting a covert American anti-drug enforcement operation. The Fugitive Predator on board attacks the three-man Army Ranger team, but the final surviving member, sniper Quinn McKenna manages to wound the creature with his own weaponry. The Predator is captured by a taskforce from Project Stargazer led by Will Traeger that arrives, while McKenna manages to escape to email several pieces of stolen Predator equipment back home, before he too is apprehended.
After he is taken back to America, McKenna is debriefed by Stargazer personnel, correctly guessing they seek to silence him for what he has seen. He is then bussed off with a group of other government captives who call themselves the "Loonies", including ex-Marine Gaylord "Nebraska" Williams, military veterans Coyle and Baxley, helicopter pilot Nettles and Lynch, another ex-Marine. Meanwhile, the captive Predator is taken to a laboratory where he is studied by Stargazer scientists, including Sean Keyes, son of Peter Keyes, Traeger and evolutionary biologist Casey Bracket. However, the creature awakens and quickly escapes, starting a rampage through the facility by slaughtering and killing soldiers who attempted to stop him. Before leaving, the Fugitive Predator finds Bracket cowering naked in a decontamination shower, but mysteriously spares her.
The Loonies witness the creature's escape and use a distraction to overpower their guards and flee the base with Bracket. McKenna reveals that he mailed the Predator equipment he stole to his wife Emily and autistic son Rory in order to keep it safe, and now fears the Predator will be heading there to retrieve it. The group rush to save McKenna's family, but upon arriving at McKenna's house where they meet Emily, they discover that Rory has already gone out wearing the recovered equipment as his costume when he found the Predator's gear.
Meanwhile after accidentally killing a man and destroying his house while trick-or-treating in hopes of avoiding detection from school bullies, Rory is cornered by a pack of Predator Dogs on a field, but McKenna, Bracket and the Loonies arrive and save him before they can attack. The Fugitive Predator appears and orders the group to drop their weapons, which they comply, but McKenna grabs his weapon and shoots at him before he and Bracket flee with Rory to his middle school to evade the Predator, but are attacked by the creature. Cornered, McKenna begins to hand back the creature's lost technology, but suddenly the Fugitive Predator is attacked by a large, hulking Predator known as the Ultimate Predator. McKenna and the others flee while the two Predators battle, but the Ultimate Predator quickly subdues the Fugitive Predator and kills him by smashing his face in before tearing out his skull and spine.
Laying low at an abandoned barn, Bracket concludes the Ultimate Predator is the result of genetic experimentation by the Predators, in which they are gathering worthy traits from other species and fusing them with their own genome to create an upgraded version of themselves. While most of the Loonies go to secure transport, McKenna, Bracket and Nebraska are captured by Traeger, who shares his theory that the Predators anticipate climate change will soon lead to the extinction of the human race and with it their ability to retrieve human DNA for further hybridization, thus they are scrambling to retrieve as much as they can before it's too late. Seeing Rory drawing a map leading to the deceased Fugitive Predator's ship, Traeger takes him away to find the vessel. McKenna, Bracket and the others escape and after they reunite with the rest of the Loonies, set off to rescue Rory with the help of a brain-damaged Predator Dog.
By the time they catch up with Traeger, Stargazer personnel have already secured the crashed Predator ship. McKenna and the Loonies launch an attack and are able to kill Traeger's men while McKenna apprehends Traeger. However, they are interrupted by the Ultimate Predator, who kills Lynch and slices a path through the Stargazer security force before he boards the vessel. Once on board, he uses Stargazer-developed translation software to inform the humans outside that he intends to destroy the craft in order to keep it out of their hands. The Ultimate Predator then offers to give them a head start before he begins hunting them.
Forced into an uneasy truce, McKenna, Bracket, Rory, the Loonies, Traeger and his remaining soldiers flee into the woods just as the ship explodes. The Ultimate Predator soon catches up and attacks them, where he tosses Baxley against a tree branch that impales him before gutting Coyle, but somehow the two men commonly shoot each other to put themselves out of their misery and also to commit suicide. Traeger arms himself with a captured Predator Plasmacaster, but accidentally kills himself with it in the process when he was distracted.
The Ultimate Predator captures Rory, apparently deeming his autism an advancement in human evolution and therefore worthwhile for Predator hybridization, and takes off in his ship. McKenna, Nebraska and Nettles jump on board, but Nettles is bisected when his legs are sliced off after the Ultimate Predator activates his ship's energy shield, causing him to fall off the ship to his death. Nebraska sacrifices himself by sliding into the engine in order to bring the vessel down and it crashes back down into the forest below. McKenna gets inside the ship and was able to save Rory before the Ultimate Predator attacks them. Bracket appears and uses a cloaking device to help McKenna fight the beast while he uses the Predator's gauntlet to fire an explosive at the Ultimate Predator's leg, causing it to blow the creature up before McKenna finishes him off with multiple shots to the head. In the aftermath, McKenna and Rory have a reunion and pay tribute to their fallen comrades with trinkets representing each one before heading off.
Sometime later, McKenna visits a scientific laboratory where Rory is now working to decode Predator technology. While there, he witnesses the opening of a pod that was ejected from the Fugitive Predator's ship before the Ultimate Predator destroyed it. A piece of technology emerges, attaches itself to a nearby worker and covers him in an armoured transformative "Predator killer" suit, before deactivating. McKenna then declares that this is his new suit.
- Boyd Holbrook as Quinn McKenna
- Trevante Rhodes as Nebraska Williams
- Olivia Munn as Dr. Casey Bracket
- Jacob Tremblay as Rory McKenna
- Sterling K. Brown as Will Traeger
- Keegan-Michael Key as Coyle
- Alfie Allen as Lynch
- Augusto Aguilera as Nettles
- Yvonne Strahovski as Emily McKenna
- Jake Busey as Sean Keyes
- Brian A. Prince and Kyle Strauts as the Fugitive Predator and the Ultimate Predator
Filming was scheduled to begin in February 2017 in Vancouver, British Columbia. On November 21, 2016, Larry Fong was confirmed hired as cinematographer for the film. Black announced that filming had began on February 20, 2017. Filming wrapped on June 2, 2017. Additional photography in Vancouver took place in March 2018. On July 6, 2018. It was revealed the film's third act was entirely re-shot due to test screenings.
Arnold Schwarzenegger talked with Black about returning as his character from the first Predator film, but declined the cameo due to the short role. Rapper 50 Cent also spoke of the possibility of being involved in the film but ended up dropping out. By September 2016, Benicio del Toro had signed on to star. The following month, Boyd Holbrook replaced del Toro, who departed due to scheduling issues. In November 2016, Olivia Munn joined the cast. In January 2017, Trevante Rhodes, Keegan-Michael Key, Sterling K. Brown, Thomas Jane and Jacob Tremblay joined the cast. In February, Alfie Allen and Yvonne Strahovski were added. In March, the last main role was filled by Augusto Aguilera while Jake Busey was also cast in a supporting role.
In March 2017, Edward James Olmos was cast as Sanchez, a military general. In August 2018, Olmos announced that his role had been cut from the final film, to reduce the film's running time, as his character was not integral to the plot.
Henry Jackman provided the musical score for the film. It also contains Alan Silvestri's theme from the film.