According to the report, the couple found it difficult to maintain their relationship with Clarke frequently going overseas to film Game of Thrones.
Clarke is also currently in rehearsals for the Broadway version of Breakfast at Tiffany's. She and MacFarlane, who hosted this year's Academy Awards, were first reported to be a couple after they were seen together at HBO's Emmy party last September, E! reports.
An email to MacFarlane's rep was not immediately returned.