"(I've got) this little urge to scratch a different kind of itch in my career, and it's just coming to the end of the character's run," Wyle told cable's "E! News Live."
Wyle, 33, will return for "E.R.'s" 11th season, premiering Sept. 23, but the actor makes no promises about a 12th season, following in the footsteps of George Clooney, Eriq La Salle, Anthony Edwards and Julianna Margulies who have already left the show.
"It feels like the show is on the edge of reinventing itself. It's time to take it to that next evolutionary place, where names like George and Tony, Eriq, Julianna and Noah are a thing of the past, and names like Shane, Linda and Parminder are a thing of the future," Wyle said, referring to new cast members Shane West, Linda Cardellini and Parminder Nagra.