The game begins in 2401 when the space marine, Sergeant Cortez, is leaving the space station that he destroyed at the end of TimeSplitters 2. His ship crash lands on the future Earth and two fellow marines greet him. Sergeant Cortez follows his squad of marines through the valley and battles unknown masked figures and TimeSplitters. Cortez is tasked with following signatures in the past that were created by time travel and thought to be caused by the TimeSplitters. He goes on a mission to go back in time to find a way to stop the TimeSplitters race from being created, with the help of Anya, The General's personal assistant.

Using his Temporal Uplink, a device connected to the Time Machine, both of which Anya has invented, Cortez travels to the year 1924. There he meets a man named Captain Ash, who seeks Cortez's help. After raiding a castle with Captain Ash, Cortez confronts an unknown man with a high concentration of Time Crystals, who then escapes with his own time machine. Cortez then travels to 1969 to stop Khallos (whom Cortez thinks is the time traveler) with the help of hippie secret agent Harry Tipper, to rescue his girlfriend, Kitten Celeste. After defeating Khallos, Anya reveals to Cortez that a mansion burned down in the 90's.