In the year 2029, John Connor (Jason Clarke), leader of the Resistance against Skynet launches a massive final offensive on Los Angeles. He is notified by his unit, Tech-Com that Skynet will attack on two fronts past and future, thereby changing warfare forever. Connor sets up two attack forces, one to strike at Skynet's main defense grid, and a second (led by Kyle Reese (Jai Courtney) and himself) to destroy Skynet's main weapon, a time machine hidden at a remote storage facility.
Before the Resistance can reach the machine, Skynet sends back a T-800, to the year 1984 to kill John's mother, Sarah Connor (Emilia Clarke). Learning of this, Reese volunteers to go back in time in order to protect her and ensure John's existence. As Kyle floats in the machine's magnetic field, he receives fragments of memories belonging to his alternate 12-year-old self (Bryant Prince) with young Sarah, including a cryptic warning of events in the year 2017. Moments before Kyle disappears, he witnesses one of the Resistance soldiers attacking John.
The T-800 arrives in 1984 Los Angeles, before confronting the three punks and demand their clothes as before in the first film. All is usual as it happened in the first film, when suddenly a voice replies "You won't be needing any clothes" gains the T-800's attention when another T-800 confronts it's younger alike. It then reveals himself as The Terminator (Arnold Schwarzenegger) who replies "I've been waiting for you". The three punks run away just as The Terminator and T-800 engage in a one on one brawl, with the former gaining the upper hand. However, Sarah arrives just in time; saving The Terminator by shooting the T-800 before it can finish his rival. Shortly after, Kyle is chased by a police officer, taking his pistol and demanding the cop tell him the date and year as before in the first film. But strangely as unlikely in the first film, the cop all ready knows Kyle's arrival and attacks, causing Kyle to open fire. The cop is revealed as the T-1000 (Lee Byung-hun), who was sent by Skynet to kill Kyle. Kyle flees before getting arrested by two more cops in the clothes store, where the T-1000 kills one of them before attacking another. Sarah then arrives to save Kyle while holding off the T-1000, who then peruses the duo, but they manage to escape. Kyle finds out that the original timeline has been altered: Sarah already knows about Skynet, Judgment Day, and Reese's role as her protector. More of which, Kyle learns that the T-800 was all ready dispatched by Sarah and The Terminator, who is now known as "The Guardian". After a brief argument between Kyle and The Guardian, who puts Kyle in the back of the van with Sarah while taking the wheel, the T-1000 attacks the trio, who plans to lure the T-1000 into a trap from a hidden building. From there, the T-1000 dispatches The Guardian and re-activates the fallen T-800, the T-1000 then peruses Sarah while Kyle fends off the T-800. After destroying it's flesh, Kyle finally destroys the T-800 by blasting it's face off. Later on, two of Kyle's approach Sarah, one of which is the T-1000, whom she shoots. Sarah then disintegrates the T-1000 with acid before The Guardian finishes him off for good.
Sarah then explains to Kyle that the Guardian was sent to protect her from the T-1000 back in 1973, where the Terminators' arrival had caused a fractured timeline that differs from Kyle's. After saving Sarah, the Guardian began training her to face her destiny. The Guardian has built a time machine similar to Skynet's and Sarah plans to use it with Kyle to travel to 1997 to change the events that would lead to Skynet's initial attack on humanity. However, Kyle, convinced that the future has changed because of his new memories, persuades Sarah and the Guardian that they should travel to 2017 instead. He believes that Skynet will begin its attack on that year of the altered timeline; Kyle and Sarah time-travel while their Guardian spends the next 33 years preparing for their arrival.
In 2017, Kyle and Sarah materialize in the middle of a busy highway and are apprehended by police. The Guardian watches from a distance and follows them to a hospital. While being treated for injuries, Sarah and Kyle learn about "Genisys", a soon-to-be-unveiled operating system that will be used on every computer system worldwide: they realize that it is Skynet's precursor. She and Kyle are then rescued by their son, John Connor. As he leads the pair to a parking garage, the Guardian appears and shoots John, who revives himself, revealing himself to be a nanomachine hybrid. John explains that shortly after Kyle was sent back, he was infected by a T-5000, and was subsequently transformed. His mission here is to ensure that the Cyberdyne Systems Corporation would receive Skynet's technology and secure its rise. John, now the T-3000, tries to convince Sarah and Kyle to join the machines and end the conflict, but they refuse. After a brief battle, the T-3000 is temporarily incapacitated with an MRI machine.
The Guardian takes Kyle and Sarah to a safe house near the Golden Gate Bridge, where they make final preparations to destroy the Cyberdyne's Genisys mainframe before it comes online. The T-3000 pursues them to the Golden Gate Bridge, where Kyle, Sarah, and the Guardian are all taken into police custody. While awaiting interrogation, the trio is freed by Detective O'Brien (J. K. Simmons), who discovers that Kyle and Sarah are time-travelers. He thanks them for saving his life from the T-800's attack back in 1984. The three hijack a helicopter on the rooftop and head toward the Cyberdyne's San Francisco headquarters, with the T-3000 in close pursuit. During the airborne chase, the Guardian dive bombs into the T-3000's helicopter, causing it to crash.
Emerging from the helicopter crash, the T-3000 enters the Cyberdyne complex and advances the countdown mechanism from 13 hours to 15 minutes. As Genisys begins to gain sentience, the Guardian, Kyle and Sarah plant bombs at key points in the facility while holding off the T-3000. After a lengthy battle, the T-3000 reveals it's true self before easily defeating the Guardian, only to be attacked by Sarah and Kyle. With not much time left, Sarah and Kyle escape while the Guardian traps the T-3000 in the magnetic field of the prototype time machine, where T-3000 manages to throw the Guardian into a vat of mimetic polyalloy liquid just beneath the magnetic field. Kyle and Sarah manage to reach a bunker beneath the facility moments before the time machine explodes, setting off the bombs, and preventing Genisys from coming online. The explosion also kills off the T-3000, destroying it once and for all. The Guardian, now upgraded with mimetic polyalloy components that the T-1000 usually has, appears and helps them find a way out of the debris.
Later, the trio travel to young Kyle's home, where they repeat the warning about Genisys to young Kyle, ensuring the events leading to their arrival. Sarah is relieved believing that she is now free to choose what to do with her future. She decides to stay with Kyle.
In a post-credits scene, it is revealed that the Genisys system core was located in a hidden subterranean chamber and has survived the explosion.