McKidd, from Elgin in Scotland, is best known for playing Owen Hunt in the medical drama, as well as Tommy in Trainspotting and Count Vronsky in the Channel 4 adaptation of Anna Karenina opposite Helen McCrory.
The actor, 42, and his wife have two teenage children.
A representative for McKidd told various US publications: “Kevin and Jane have jointly decided to end their marriage. They look forward to continuing to co-parent their children, who have been their top priority, and will to continue to enjoy a close and caring relationship.”
McKidd has starred in Grey’s Anatomy since 2008 and directed episodes of the show. He will next be seen on the big screen opposite Alicia Vikander and Cara Delevingne in Tulip Fever.