Chambers, 49, one of only four original cast members to remain a series regular for the 16th season, announced he will not be returning to the medical drama after last being seen in the 350th episode of "Grey's Anatomy," which aired Nov. 14.
"There's no good time to say goodbye to a show and character that's defined so much of my life for the past 15 years," Chambers said in a statement to Deadline.
"For some time now, however, I have hoped to diversify my acting roles and career choices."
Chambers' exit was confirmed by ABC.
Dr. Alex Karev, Chambers' character, was last seen leaving his position as chief of staff and chief of surgery at Pacific Northwest General Hospital to take care of his ailing mother.
"As I move on from 'Grey's Anatomy,' I want to thank the ABC family, Shonda Rimes, original cast members Ellen Pompeo, Chandra Wilson and James Pickens, and the rest of the amazing cast and crew, both past and present, and, of course, the fans for an extraordinary ride," Chambers said.
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