Mitch Pileggi is promoted to regular cast member, having been recurring in the role as Walter Skinner since near the end of the first season. Annabeth Gish is promoted to regular as Monica Reyes, having appeared in a recurring role in the previous season.
Although this ended up becoming the last season of the original run, it was originally intended for it to carry on but with John Doggett and Reyes as the main characters replacing Mulder and Scully. But The X-Files franchise wouldn't return until 2008 with the second feature length film The X-Files: I Want to Believe, which eight-years later would be followed by by a revival event series - 14 years since the show last broadcast on television.
|"Mulder? Where are you?"|
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|No.||Episode Name / Summary|
|9ABX01||"Nothing Important Happened Today"
Although Scully has returned to her teaching position at the FBI Academy in Quantico, Agent Doggett asks for her help as he investigates the death of an EPA official who died after his car was forced off a bridge by a woman he picked up.
|9ABX02||"Nothing Important Happened Today II"
Scully, Doggett and Reyes are led to a ship where they find evidence of experimentation on human embryos.
Scully helps Reyes and Doggett investigate a series of bizarre killings that seem to be due to demonic possession but which Doggett believes is a hoax.
When Doggett is shot and hospitalized with severe injuries, all evidence points to Reyes as his attacker.
|9ABX05|| "Lord of the Flies"
When an amateur stunt performer is killed while performing a daring act for a local cable reality show, Scully, Doggett and Reyes discover that the culprit was apparently a swarm of killer flies hidden in the victim's brain.
|9ABX06||"Trust No 1"
Scully tries to arrange Mulder's return but learns that the forces against them are unrelenting.
Reyes and Scully struggle to locate Doggett after he wakes up in Mexico with no memory of who he is or how he got there.
Reyes discovers she is somehow connected to a series of murders in which each victim is skinned alive.
Scully, Doggett and Reyes find evidence of a dangerous UFO cult which has found a second spacecraft similar to one Scully studied in Africa two years ago. Misled by the FBI, the agents enlist the help of the Lone Gunmen to protect Scully's son after they learn that the UFO cult apparently intends to kill the child.
As Doggett recovers from injuries in hospital, Reyes and the Lone Gunmen help Scully in an effort to recover her baby.
After Reyes is involved in a serious car accident and subsequently hospitalised, Doggett meets a woman who works at the hospital who claims that she can contact his seemingly deceased partner.
Doggett struggles to accept new evidence which seems to suggest that a man he arrested as a killer thirteen years ago was actually innocent.
While investigating a serial killer who uses numerology to choose his victims, Reyes and Scully meet an unusual man who may prove more of a hindrance than a help.
Leyla Harrison, an FBI agent with a passion for the X-Files that Mulder and Scully investigated, alerts Scully, Doggett and Reyes to a case she believes is an X-File involving a young boy with an overactive imagination.
|9ABX15||"Jump the Shark"
When former Area 51 Man-in-Black Morris Fletcher appears, claiming that a female friend of the Lone Gunmen is actually a super-soldier, Doggett and Reyes attempt to locate her but find that the situation is graver than they first expected.
Scully, Doggett and Reyes find a disfigured man whose DNA results say that he is Mulder, but other details is completely different. They soon learn he is actually Jeffrey Spender, returning from a bunch of tests on him.
A particularly adept student from Scully's class at the FBI Academy helps to finally solve the murder of Agent Doggett's seven-year-old son.
Scully, Doggett and Reyes find a man who seems obsessed with The Brady Bunch and has extraordinary mental powers.
Mulder is discovered looking for classified information at an army base and, after allegedly killing an apparently indestructible super-soldier, he is placed on trial to defend the X-files.
- Gillian Anderson as Special Agent Dana Scully (20/20 episodes)
- Robert Patrick as Special Agent John Doggett (20/20 episodes)
- Annabeth Gish as Special Agent Monica Reyes (20/20 episodes)
- Mitch Pileggi as Assistant Director Walter Skinner (11/20 episodes)
- David Duchovny as former Special Agent Fox Mulder (2/20 episodes)
- James Pickens, Jr. as Deputy Director Alvin Kersh (7/20 episodes)
- Nicholas Lea as Alex Krycek (2/20 episodes)
- Cary Elwes as Assistant Director Brad Follmer (6/20 episodes)
- Tom Braidwood as Melvin Frohike (5/20 episodes)
- Bruce Harwood as John Fitzgerald Byers (5/20 episodes)
- Dean Haglund as Richard Langly (5/20 episodes)
- Alan Dale as Toothpick Man (4/20 episodes)
- Adam Baldwin as Knowle Rohrer (3/20 episodes)
- Jeff Gulka as Gibson Praise (2/20 episodes)
- Sheila Larken as Margaret Scully (2/20 episodes)
- Lucy Lawless as Shannon McMahon (2/20 episodes)
- Chris Owens as Jeffrey Spender (2/20 episodes)