The X Files starts with a scene showing North Texas during 35,000 B.C. It shows a hunter encountering an extraterrestrial being inside a cave. The alien and the caveman fight. The caveman wins but not after the creature has infected him with a black oil-like substance. Fast forward to the year 1998. A group of boys are seen digging a hole on the same area where the caveman died. There, one of the boys falls on the hole. After the fall, Steve discovers a human skull. He examines the bone and a black substance oozes out and penetrates his skin. The thing travels inside his system until it reaches his head and turns his eyes black. When he does not come, four firefighters come to his rescue but the men do not come out of the hole as well. It is as this moment that men wearing biohazard suits arrive.
In Dallas, former X-Files and FBI Special agents Fox Mulder and Dana Scully are handling a bomb threat case against a federal building. Mulder searches for the bomb and finds it in a vending machine. Mulder and Scully head the evacuation process while Special Agent in Charge Darius Michaud is left behind to disarm the bomb. Unbeknownst to Mulder and Scully, Michaud does not try to disengage the bomb and it eventually explodes.
Upon their return to Washington D.C., Mulder and Scully are blamed for the additional four casualties after the investigation of the explosion. They are set to attend hearing where their capabilities as agent will be assessed and evaluated. Adding to the craziness of the events is Mulder meeting a certain doctor named Alvin Kurtzweil who claims that the four other victims of the explosion are already dead even before the bomb exploded. Kurtzweil claims that the explosion should have destroyed the bodies as well the real cause of the deaths of the victims. Scully manages to examine one of the bodies and find traces of alien virus.
Mulder and Scully decide to investigate the case. They go to Texas where the victims were originally found. They arrive finding a train delivering tanker trucks to a large cornfield sandwiched between two glowing domes. They check but the domes are empty. A few moments later, they are chased out by a swarm of bees and once outside, black helicopters start pursuing them.
After their escape, Mulders tries to seek help from Kurtzweil while Scully hears the news of her transfer to Salt Lake City, Utah. Before the two agents say goodbye to each other, Scully is stung by a bee and she faints. Mulder calls for paramedics and when the ambulance arrives, the driver shoots him in the head and takes Scully away. Mulder regains consciousness in the hospital. It turns out that the bullet just grazed him on the temple. As he tries to search for Scully, he encounters again the Well-Manicured Man who informs him Scully’s location in Antarctica. He also provides Mulder with the vaccine for the virus. After their meeting, the Well-Manicured Man is killed by a car explosion. It is discovered that he is part of a covert organization called The Syndicate.
When Mulder goes to Antarctica, he discovers a hidden underground laboratory managed by the Cigarette Smoking Man. Mulder injects the vaccine to Scully and the upsets the atmosphere inside the laboratory. The disturbance awakens the hibernating cocooned aliens. Before they can be fully awaked, Mulder and Scully escape and the lab is destructed. They discover that the lab is only a part of a gigantic extraterrestrial spaceship buried under the snow. The machinery of the vessel continues to run and spaceship shoot up from the snow and disappears into the sky.
At the end, Mulder and Scully’s investigation about the case is covered up. The bee that stung Scully is the only thing left from their alien exploration. Scully hands the evidence over to the Lone Gunmen, not failing to mention that the FBI is currently unequipped to investigate such things. The movie ends with the Cigarette Smoking Man warning Strughold about Mulder. He hands over a telegram informing him that the X-files unit has been reinstated.