The actor, 47, announced the news on the That's Awesome! With Steve & Bradford podcast this week.
"I’ve finished my reign at Days," Vaughan told the hosts, who used to star alongside him on General Hospital.
"For all my Days fans that are listening, I love you all... it's never over, so I'm not gonna say it's over," he said. "I’m taking a break, if you will."
"Days was going through a renewal negotiation and not knowing where they were going to go," he said, adding, "I just felt my time was coming to an end anyways."
Vaughan has portrayed Eric Brady on the soap opera since 2012.
The long-running NBC daytime soap was renewed for a 56th season in November of last year, a week after it was reported that all of the actors on the show were reportedly released from their contracts and the show was going on an "indefinite hiatus."
A source confirmed to PEOPLE at the time that it was likely that the soap would continue.
"The show shoots months and months in advance and they’ve gotten so far ahead that the cast was prepared ages ago for the fact that they would all be put on hiatus until closer to pick-up (aka renewal) time, for scheduling reasons," the source said.
It will be the second marriage for both Vaughan and Harmon, 47, who split with ex-husband Jason Sehorn in 2014. She shares three daughters with the NFL player. Vaughan divorced Dutch model and actress Touriya Haoud that same year, and shares three sons with her.
In May, Vaughan shared a sweet tribute to Harmon on Mother's Day, sharing a photo with the actress and writing in the caption, "TRULY BLESSED."