The two-time Golden Globe winner just finished work on the final season of his Showtime hit, Californication, which premieres this month.
With help from a young partner, Duchovny's character will take part in a "complicated undercover operation" of Manson's group, though it won't get to the Manson family's murder spree until later seasons.
The 53-year-old actor previously worked with NBC entertainment chair Robert Greenblatt on The X Files.
“I’m thrilled to be working with Bob Greenblatt again and coming back to broadcast television. I think Aquarius has a chance to be a special show and I can’t wait to get going,” Duchovny said in a statement.
"I know there is a big audience waiting to see him," Greenblatt said.