A source told People that the couple had been living apart for some time while trying to salvage the relationship, but it seems it was all for naught.
Wilde, 26, and Ruspoli, 35, eloped in Virginia six months after meeting when Wilde was 18. They later had an official wedding.
Ruspoli is a filmmaker based in Los Angeles. His family owns the Palazzo Ruspoli in Rome and a castle in Vignanello, Italy.
The House actress is next set to be seen on the silver screen in two big summer releases: she'll be fighting interstellar visitors alongside Daniel Craig and Harrison Ford in the sci-fi action flick Cowboys & Aliens and getting laughs with Jason Bateman and Ryan Renyolds in The Change Up.