The film opens in 35,000 B.C., in what will become North Texas. Two cavemen hunters encounter a large extraterrestrial life form in a cave, which kills one and infects the other with a black oil-like substance. In 1998, in the same area, a boy falls into a hole and is also infected by a black substance which seeps from the ground. Firefighters who enter the hole to rescue him do not come out. A team of men wearing hazmat suits arrive and extract the bodies of the boy and the firefighters. Meanwhile, FBI Special Agents Fox Mulder and Dana Scully, while investigating a bomb threat against a federal building in Dallas, discover the bomb in a building across the street. As the building is evacuated, Special Agent in Charge Darius Michaud remains, ostensibly to disarm the bomb. However, he simply waits for the bomb to detonate.
Mulder and Scully are later chastised because, in addition to Michaud, four other people were in the building during the bombing. That evening Mulder is accosted by a paranoid doctor, Alvin Kurtzweil, who explains that the "victims" were already dead, and that the bombing was staged to cover up how they died. At the hospital morgue, Scully is able to examine one of the victims, finding evidence of an alien virus. Meanwhile, the Cigarette Smoking Man goes to Texas, where Dr. Ben Bronschweig shows him one of the lost firefighters, who has an alien organism residing inside his body. He orders Bronschweig to administer a vaccine to it, but to burn the body if it fails. Later, the alien organism unexpectedly gestates and kills Bronschweig. Mulder and Scully travel to the crime scene in Texas, where they find the site has been hastily turned into a new playground and encounter the boys whose friend fell into the hole. Following their direction, the pair follow some white gasoline tankers to a large cornfield surrounding two glowing domes. Inside the domes, grates in the floor open and swarms of bees fly out. The agents flee, chased by black helicopters, but manage to escape.
After returning to Washington, D.C., Scully attends a performance hearing, after which she is transferred. Mulder is devastated to lose his partner. The two are about to share a kiss when Scully is stung by a bee which had lodged itself under her shirt collar; she quickly falls unconscious while Mulder calls paramedics, but the driver of the ambulance shoots Mulder and whisks Scully away. Mulder, not severely injured, slips out of hospital with the help of The Lone Gunmen and FBI Assistant Director Walter Skinner. He then meets a former adversary, the Well-Manicured Man, who gives him Scully's location, along with a vaccine against the virus that has infected her. As Mulder leaves, the Well-Manicured Man kills himself in a car bomb, before his betrayal of The Syndicate is discovered.
Mulder finds Scully underground in Antarctica, in a large facility containing many humans in ice-like enclosures. He breaks Scully's confinement and uses the vaccine to revive her, but this disrupts the facility and cocooned aliens begin trying to escape. Just after the agents escape to the surface, a huge alien vessel emerges from beneath the ice and travels into the sky. Mulder watches it disappear into the distance as Scully regains consciousness. Some time later, Scully attends a hearing, where her testimony is disregarded and the evidence covered up. She hands over the only remaining proof of their ordeal, the bee that stung her, noting that the FBI is not currently capable of investigating this evidence. Outside, Mulder reads an article that has covered up the domes and crop field in Texas; Scully informs Mulder that she is willing to continue working with him.
At another crop outpost in Tunisia, the Cigarette Smoking Man warns Conrad Strughold that Mulder remains a threat, as he explains what Mulder has found out about the virus. He then hands him a telegram revealing that the X-files unit has been re-opened.
David Duchovny as Special Agent Fox Mulder
Gillian Anderson as Special Agent Dana Scully
Martin Landau as Alvin Kurtzweil
Blythe Danner as Jana Cassidy
Armin Mueller-Stahl as Conrad Strughold
Mitch Pileggi as Assistant Director Walter Skinner
William B. Davis as Cigarette-Smoking Man
John Neville as Well-Manicured Man
Dean Haglund as Richard "Ringo" Langly
Bruce Harwood as John Fitzgerald Byers
Tom Braidwood as Melvin Frohike
Jeffrey DeMunn as Ben Bronschweig
Jason Beghe as FBI Man at Bomb Site
Michael Shamus Wiles as Black-Haired Man
Terry O'Quinn as Special Agent in Charge Darius Michaud
Lucas Black as Stevie
Gary Grubbs as Fire Captain Cooles
Nick Lashaway as Young Fox Mulder
also known as The X-Files: Fight the Future
based on Chris Carter's television series of the same name