Responding to a tweet about the news, which proclaimed that "#GreysAnatomy is about to feel one of its biggest losses yet", the actress, 50, shared that she couldn't agree more.
"Truer words have never been spoken," Pompeo wrote of her fellow original cast member, including a broken heart emoji.
ABC confirmed to people.com on Friday that Chambers had left the show after 16 seasons.
"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.
"For some time now, however, I have hoped to diversify my acting roles and career choices. And, as I turn 50 and am blessed with my remarkable, supportive wife and five wonderful children, now is that time."
Chambers added: "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."
His last episode aired on November 14. He was absent from the mid-season finale and it was explained that he was taking care of his ailing mother.
( With inputs from IANS )