Theron, 39, and Penn, who got together in December 2013, had apparently started living separately and called it quits, reported People.
According to sources, Theron and her son three-year-old son Jackson lived at their Hollywood home and Penn, 54, at his Malibu mansion, which he had put up for sale but recently pulled off the market.
The couple backed out of at least one scheduled event together before Theron headed to London to film "The Huntsman".
However, representatives for the stars have not commented on the split.
Penn was spotted solo in the Brentwood section of Los Angeles recently, purchasing magazines and cigarettes from a local newsstand.
Just last month, Theron had raved about her partner to British Elle, calling him the "love of my life.