The sixth season of the science fiction television series The X-Files commenced airing on the Fox network in the United States on November 8, 1998, concluding on the same channel on May 16, 1999, and consisted of twenty-two episodes.

The season continued from the 1998 feature film and focused heavily on FBI federal agents Fox Mulder (David Duchovny) and Dana Scully's (Gillian Anderson) separation from the X-Files Division and the demise of the Syndicate—a "shadow government" group attempting to cover up the existence of extraterrestrials—in the two-part episode "Two Fathers" and "One Son".

The first half of the season also saw Mimi Rogers and Chris Owens' characters—Diana Fowley and Jeffrey Spender, respectively—become recurring characters.

Assistant Director Walter Skinner (Mitch Pileggi) tells Mulder that he and Scully have been denied reassignment to the division.

Mulder goes to his former basement office, only to discover that Jeffrey Spender (Chris Owens) and Diana Fowley (Mimi Rogers) have been assigned to the X-Files.

Going against orders, Mulder and Scully track down an escaped alien in Phoenix, Arizona while Cigarette Smoking Man (William B. Davis) gives chase.

Mulder and Scully eventually discover that Cigarette Smoking Man has been using Gibson Praise to locate the creature.

The culprit is revealed to be Alex Krycek (Nicholas Lea), a rogue FBI agent who formerly worked for the Syndicate, who continues to control the potentially debilitating nanotechnology in Skinner's system in order to achieve his goals.

Cassandra later escapes from a hospital and arrives at Mulder's apartment, demanding that he shoot her because she is the embodiment of fifty years of work by the Syndicate—an alien-human hybrid that will trigger colonization if the aliens learn of her existence.

[3] Fowley arrives and forcibly takes Mulder, Cassandra, and Scully to a CDC facility at Fort Marlene.

The move was instigated by David Duchovny, who portrayed Mulder, in order to increase his opportunity to find movie work as well as to give him a chance to be nearer to his wife, Téa Leoni.

[10][11] According to Andy Meisler, "The very first shot of the season, a long look directly into a bright sun shining on a barren desert, was designed to boldly announce the show's arrival in Southern California.

"[12] As a result of the move, the episode featured a largely new group of crew members, hired by Carter, Frank Spotnitz and new co-executive producer Michael Watkins; this necessitated the show's new crewmembers spending five weeks, receiving, unpacking, and cataloging filming material from their Vancouver counterparts.

Many accused the show of "Hollywood-izing" the series by adding notable guest stars as well as making the plots simpler and more enjoyable for larger audiences.

Bruce Harwood, who played Lone Gunman John Fitzgerald Byers noted, "At the time, the exchange rate between Canadian and U.S. dollars was pretty dramatic.

[…] It became apparent very quickly to me that we were no longer going to have things such as nuclear submarines descending through the ice and trains exploding in the middle of the woods".

However some fans were alienated by the show in its sixth season, due to the different tone taken by most stand-alone episodes after the move to Los Angeles.

[30][31] The "Two Fathers"/"One Son" story-arc, which featured the destruction of the Syndicate, was called one "of the most coherent, [...] almost unbearably tense, hours in the series' run" by one critic.

[32] Finally, the Duchovny-penned "The Unnatural", which featured the story of an alien who fell in love with baseball, was praised by critics for its plot, directing, and originality.