UsMagazine.com reported the news Wednesday, but did not offer details regarding why or when Duchovny and Leoni called it quits.
The parents of a 9-year-old son and 12-year-old daughter previously split up for several months in 2008 while Duchovny underwent treatment for sex addiction. The couple later reconciled.
Duchovny is best known for his work on TV's "The X Files" and "Californication."
Leoni has appeared in the films "Fun with Dick and Jane," "Family Man," "Jurassic Park III" and "Spanglish."