"The Sixth Extinction" earned a Nielsen household rating of 10.6, being watched by 17.82 million people in its initial broadcast.

The show centers on FBI special agents Fox Mulder (David Duchovny) and Dana Scully (Gillian Anderson) who work on cases linked to the paranormal, called X-Files.

In the episode, Assistant Director Walter Skinner (Mitch Pileggi) and Michael Kritschgau (John Finn) work desperately in an attempt to discover what is wrong with Mulder, whose abnormal brain activity has rendered him imprisoned in his own head, but they are unaware of Agent Diana Fowley’s (Mimi Rogers) duplicity.

The episode was written due to series creator Chris Carter's fascination with the possibility that extraterrestrials were involved in the great extinctions that had happened millions of years ago.

On the coast of Côte d'Ivoire, Scully sits in her tent studying detailed photographs of the spacecraft half-buried in the beach nearby.

A figure, the Primitive African Man, mysteriously appears before suddenly vanishing, after which Scully's tent is swarmed by flying insects.

Once there, Kritschgau believes Mulder has alien-induced mind reading abilities and injects him with phenytoin to slow down his brain activity.

Spotnitz said of the end result, "For me, it was a lot like a fifties monster movie with Scully out on the beach with this guy going nuts with a machete, the bug attacks, and the sea of blood.

To create the scene in which a huge number of insects swarm Scully's tent, popcorn and foam peanuts were blown by a large fan onto the soundstage; images of crickets were then digitally composited on top of the detritus during post-production.

[2] A large portion of the episode was based on the ancient astronaut theory, which proposes that intelligent extraterrestrial beings have visited Earth in antiquity or prehistory and made contact with humans.

[3] Frank Spotnitz was astounded at how little negative fan mail the show received, despite the fact that the "Biogenesis"/"The Sixth Extinction"/"Amor Fati" story arc heavily hinted that aliens were the originators of the notion of God and religion.

Tucker praised series creator Chris Carter's writing ability, stating that "the kickoff episode suggests the author's limitless imagination for sustaining his alien-nation tropes".

[12] Robert Shearman and Lars Pearson, in their book Wanting to Believe: A Critical Guide to The X-Files, Millennium & The Lone Gunmen, rated the episode three-and-a-half stars out of five.

[13] Den of Geek writer Nina Sordi ranked "The Sixth Extinction," along with "Biogenesis" and "The Sixth Extinction II: Amor Fati," as the fifth best episode of the series, writing, "it is evident that as [The X-Files] progressed, the episodes surrounding those storylines and the breaking points Mulder and Scully endured push them further and further towards total, irreversible defeat.

"[14] Monica S. Kuebler of Exclaim magazine called "The Sixth Extinction", along with "Biogenesis" and "Amor Fati", one of the "best" episodes during the show's "colonization" phase.

[15] Kenneth Silber of Space.com wrote positively of the episode, hoping that it foreshadowed answers to come, writing "As the middle installment of a three-part story and what was then thought to be the final season premiere of The X-Files, 'The Sixth Extinction' is suffused with a somber pre-apocalyptic mood, but one vivified by the possibility that soon we'll have answers to the most important outstanding mysteries of the series.