The actor, who plays Dr Mark Sloan - otherwise known as 'McSteamy' - has decided to leave the medical drama to pursue other opportunities.
Speaking to TVLine, Dane said: "I am extremely grateful to everyone at Grey's, ABC and Shondaland for the experience and memories I have had over the course of this run.
"It has been wonderful to work alongside and learn from a creative force such as Shonda Rhimes."
The end of last season saw Dr Sloan's soul mate Lexie pass away from injuries suffered in the plane crash, which caused Sloan to suffer a cardiac arrest, only to be saved by quick-thinking Cristina (Sandra Oh).
At the time, showrunner Shonda Rhimes hinted that more departures could be on the horizon, saying: "Just because you saw people alive at the end of the finale doesn't mean they're going to be alive when the season starts up."
Rhimes hailed Dane in a statement, calling 'McSteamy' - Dr Sloan's affectionate nickname on the show - "one of the most beloved characters on Grey's Anatomy".
She added: "We're a big family here at Grey's with a long history together and Eric will always remain an important part of our family.
"I wish him the best and I look forward to watching him as he continues to steam up the big and small screen."
Watch Lexie profess her love for Mark in the last season of Grey's Anatomy below: