Collins will not appear in the CW drama's seventh season as a series regular and is currently only expected to feature in the first two episodes.
"It was a long time coming," he told E! Online. "[I have] mixed feelings about it. It's exciting to have other prospects now and it's fun to do other roles.
"I'm looking forward to doing some other stuff [but] I will miss the old crew up on Supernatural in Vancouver."
Collins also suggested that Castiel will no longer provide the show's "comic relief" in the new season.
"I'm not playing the 'fish out of water' sidekick anymore," he said. "That element is gone.
"It's one of the things that's great about the show. They don't rest on their laurels. Just because something is working, doesn't mean they keep doing it. They like to change it up and try something new [so] it doesn't get stale and that's cool."
Supernatural star Jensen Ackles previously told Digital Spy that Castiel's relationship with Sam and Dean Winchester could be damaged beyond repair.
Supernatural will return to Fridays at 9/8c on The CW from September 23.
> Supernatural Misha Collins: 'Castiel is a vengeful god'
Watch Jim Beaver discuss Supernatural with Digital Spy below: