The film opens ten years after the previous 'Pacific Rim' movie after the so-called the Battle of the Breach, in which humanity defeated the Kaiju monsters by sealing the entrance into our world. Jake Pentecost (John Boyega) is the son of Stacker, but he doesn't see himself as anything like his dad. Jake is a former Jaeger cadet who now makes a living by dealing Jaeger parts in exchange for goods.
Jake goes to a decommissioned Jaeger scrapyard with three thugs that he's hustled in search of a very valuable Jaeger core. The thug leader forces Jake at gunpoint to find it to pay off what he stole from him. Jake finds that the core is missing, but his tracker is picking it up. He tricks the thugs into a trap and chases after someone who already has the core. Jake finds that it's an orphan girl, Amara Namani (Cailee Spaeny). As the authorities arrive, Amara boards a Jaeger she built and calls Scrapper, and Jake follows. A Pan-Pacific Defence Corps Jaeger, November Ajax, chases after the two, but Amara pilots Scrapper to get them out. Jake tells her to use one of Scrapper's batteries to disable November, which works briefly, but the two are caught anyway.
Jake and Amara are in a cell when Jake is called in to speak to Mako Mori (Rinko Kikuchi), who is the PPDC's General Secretary and Jake's adopted sister. She gives Jake a choice between going to jail or training new Jaeger cadets. Jake makes up his mind, and Mako says he's already set, and that Amara will be a cadet too.
The two are sent to the Hong Kong Shatterdome to begin training. Jake meets his former co-pilot in Gipsy Avenger, Nate Lambert (Scott Eastwood), with whom he now has a strained relationship with. Amara then learns that Jake is Stacker's son, as she is a fan of him and Jaegers in general. Jake also meets Jules Reyes (Adria Arjona), a soldier that he becomes attracted to. Nate takes Jake and Amara to meet the other cadets, including Suresh (Karan Brar), Ilya (Levi Meaden), and Viktoria (Ivanna Sakhno), or "Vik". She isn't happy that Amara has gotten into the program based off the PPDC being impressed by her building her own Jaeger, when it took Vik three tries to get in.
The cadets begin their training by testing out their Drift compatibility. Amara doesn't do well at first and is discouraged. Jake and Nate talk in the kitchen and agree to stay out of each others' way.
The Shatterdome is visited by reps from Shao Corporations, including its CEO Liwan Shao (Jing Tian) and Newt Geiszler (Charlie Day), who is now her Head of Research and Development. Their plan is to quickly deploy a large number of Jaeger drones around the world, which is viewed as a threat to the PPDC. Newt reunites with Hermann Gottlieb (Burn Gorman), who brings him to the PPDC's research lab to show him a vial of Kaiju blood, which may be essential in the development of the drones in making thruster pods. Hermann also tells Newt that he still has nightmares of when they drifted with the Kaiju brain. Newt then leaves to go reunite with Liwen, who tells him to stay away from Hermann so that she doesn't have to question his loyalty.
Mako tells Jake how she doesn't trust the drone program because they are remote-operated and could be compromised or hacked. She tells him that she had it authorized for Jake to co-pilot Gipsy Avenger at an upcoming meeting in Sydney.
Gipsy Avenger gets deployed in Sydney with Jake and Nate co-piloting. Suddenly, a rogue Jaeger, Obsidian Fury, rises from the ocean and begins to attack. Jake and Nate operate Gipsy to fight back. In the chaos, a chopper with Mako on-board is struck by Obsidian, and although Gipsy tries to rescue her, they just miss her, and the chopper crashes to the ground. Obsidian returns to the water.
Jake returns to the PPDC, mourning Mako's loss. He meets with Amara, who offers her condolences. In order to help her out, Jake drifts with Amara, and he sees a memory of hers. She was on a boardwalk with her parents and brother when a Kaiju began to attack. When Amara tried to reach her family, they were crushed by the Kaiju. Jake has to snap her out of it and remind her not to hold on to the memory.
At the Shao headquarters, Newt learns from Liwen that the drone program has been authorized in the wake of the Sydney attack. Newt considers the timing of this to be inconvenient. He returns home and starts talking to someone he calls Alice. Turns out "Alice" is a Kaiju brain in a pod that Newt frequently drifts with.
At the PPDC, Amara and Vik get into a fight, with Amara actually managing to overpower Vik despite being half her size. The fight is broken up immediately by Nate. Jules enters to tell him that Hermann deciphered Mako's final message. It's the location of an old Jaeger facility in Zemlya where Obsidian may be operated from.
Jake and Nate ride Gipsy to the facility, where Obsidian attacks again and destroys the facility. The two manage to overpower Obsidian this time and rip out its central core. Gipsy pulls off Obsidian's head to reveal that it was being operated by a Kaiju brain.
Amara and a few cadets sneak into the wreckage of Obsidian Fury. Upon inspection, Amara finds a tube with a Shao logo on it. As she cuts into it, it leaks acid that severely burns another cadet's arm. She is subsequently kicked out of the program, to her disappointment. After she expresses that she doesn't belong, Jake tells her not to let what other people think of her define her. As Amara leaves, the other cadets express their regret, and Vik sincerely tells her to build her next Jaeger bigger.
The drones are set to be deployed to PPDC Shatterdomes around the world. However, they are quickly taken over by Kaiju brains, making them look like Jaeger-Kaiju hybrids. They begin to attack the Shatterdomes, killing many and wrecking almost all the other Jaegers. Hermann rushes to find Newt to stop this, but when they reach the lab, Newt initiates a program in the drones to prepare them to open Breaches around the world to unleash more Kaiju. Newt has been planning this for the last decade after his mind has been corrupted by Precursors (Kaiju creators) after drifting with the Kaiju brains for so long. Hermann tries to stop him, but Newt gets away. The drones begin to open the Breaches, and Kaiju start to crawl out from the ocean depths. Liwen manages to shut the drones down and keep the Breaches closed, but three Kaiju have successfully gotten out and are making their way into Japan.
In the lab, Hermann and the others determine that the Kaiju are headed to Mt. Fuji because it contains rare earth elements, and when mixed with Kaiju blood, will create a violent reaction that sets off the Ring of Fire and activates all nearby volcanoes to destroy humanity and bring forth more Kaiju. The PPDC gets set on bringing in reinforcements to repair Jaegers and get the cadets ready for battle.
Jake and Nate meet with the cadets and prepare them with a speech from Jake, much like his father did in the past. He and Nate board Gipsy Avenger, while Amara joins Vik and another cadet in Bracer Phoenix, along with Guardian Bravo and Saber Athena joining. They lift off using Hermann's rocket thrusters with the Kaiju blood and rare earth elements as fuel.
The three Kaiju are already attacking the city. The Jaegers arrive and start fighting back. Unfortunately, Newt uses his tech to merge the beasts into one Mega-Kaiju. This one proves to be insanely powerful, causing casualties within Guardian and Saber. It manages to overpower all the Jaegers before it starts heading toward Mt. Fuji. Nate is severely injured, and Bracer is down as well. Nate ejects himself to allow Amara to join Jake for them to co-pilot Gipsy. Liwen arrives with Scrapper and uses the last rocket to help Gipsy head toward Mt. Fuji.
The Mega-Kaiju moves closer and closer toward the volcano. The cadets decide the only way to stop it is to send Gipsy soaring right into it. Once they reach a high enough altitude, Gipsy is sent hurtling toward the beast. Jake and Amara struggle to free themselves, but Scrapper gets them out in time. Gipsy collides powerfully with the Mega-Kaiju, sending it rolling down the mountain until it dies. Newt tries to initiate Plan B, only to get knocked out by Nate. Jake and Amara land safely and celebrate their victory.
The last scene shows Newt in custody, vowing revenge and swearing that the Kaiju will return and that the Precursors will destroy the world. Jake enters and promises that humanity will be ready to fight back, bigger and badder than ever.