Hall, 39, and Carpenter, 31, released a joint statement announcing the split a day after reports surfaced that Carpenter attended the show's fifth-season finale party without Hall.
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"Having been separated for some time, Jennifer Carpenter and Michael C. Hall have filed for divorce," it said.
Reps for both said that the divorce was "amicable."
The couple, who met on the set of the show, were married on New Year's Eve 2009.
Carpenter was by Hall's side as he fought Hodgkin's lymphoma over the past year.