The actor, who plays Rory Brown, Mrs Brown's gay son, announced the news in a newspaper interview.
Speaking to The Irish Daily Mail he said "I hadn't been happy working for the Mrs Brown's Boys company for the last 18 months to two years."
Cowan has been acting alongside creator Brendan O'Carroll since he first devised the character in the 1990s. He performed his final show with him last night [Sunday 9th July] at the O2 Arena.
Speaking to the newspaper he explained: "I feel that 26 years is enough so I decided it was time to go. I told Brendan on June 16th about my decision to leave. That's when I handed in my notice. I was supposed to leave at the end of that week, but Brendan said that would be impossible and asked if I'd stay on until the end of the London O2 gigs. So I agreed to that."
Cowan refused to divulge exact details of why he was quitting [he has since explained he was bored, see update below]. The newspaper quotes him as saying: "I'm not going into details about why I was unhappy. I did the final show, packed my stuff into a small Waitrose plastic bag and just left the venue."
The actor didn't have a formal leaving party. He posted a picture on his Twitter account today showing him out for dinner last night with a group including Gary Hollywood, who played his partner Dino Doyle in the show, and EastEnders actor Adam Woodyatt.
Cowan says he has not yet made plans as to what he wants to do next, but did suggest: "I'd love to do something like a weekend radio show but we'll see what comes down the line. For now I'm going to take a little time off."
11th July update - Cowan explains he was 'bored':
Rory's agent told The Mirror: "Touring is a young man's game and he just wanted to take some time off to reassess what he would do with the rest of his life. It was an amicable split and he has worked with Brendan for years so there was no hard feelings."
Brendan O'Carroll released a statement to say: "To all of us it feels like Ronaldo leaving Manchester United. But Ronaldo went on to amazing success which I know Rory will too. I can't even quantify the contribution Rory has made to our success and the well-being of me and my family, not just on screen or stage but way before that as a friend and a driving force in getting us here."
Meanwhile the actor himself has explained his reasons in an interview with The Mirror. Speaking about touring, he said: "I got tired of it, I haven't been happy for the last two years working there. There was no row with Brendan, there was no dispute over money or anything - in fact quite the opposite. I got so well paid it enabled me to be able to leave, I didn't need to stay.
"What was killing me was we were doing the exact same arenas in the exact same order we did two years ago. I would have known week-by-week where I'd be until 2022 - and it's not like they're different every year, it's the same thing. We're so big now that years are scheduled out."
Talking more about his final performance, he explained: "Brendan announced at the end of the show, 'Give a round of applause to Rory, it's his last show'. I think they thought it was a joke at first but then they realised it wasn't. There was loads of aahs and people saying 'don't go' but my mind was made up. My last show was the O2 in London, six sold-out shows, 10,000 people at each show, it was brilliant - if you're going to go out on a high you can't get much bigger."
The actor also reflected in the interview about the "incredible" journey the show has taken. "I started to work with Brendan 26 years ago as his publicist when he was playing pubs. To go from pubs and hoping you'd get 100 people in, to playing arenas with 10,000 people a night and everything in between that we've done, it's been fabulous."
"I couldn't get over the reaction on my social media - there was one from an old woman and it brought tears to my eyes when I read it. She said, 'Oh my god, it's not true, I'm 78 years of age, this is like losing a member of the family'. One half of me wanted to say to her, 'Ah come on, it's only a television show' but the other half sort of hit me how much the show means to people, so that was really sad."
He concluded: "It was becoming a chore for me, doing the same thing. I loved the show but that's only two-and-a-half hours a day five days a week. I'd a great time on stage with Brendan, we really had a laugh. You see I'm not a trained actor, so Brendan used to know if he did something funny I'd laugh and he'd go out of his way to have me in convulsions of laughter." He concluded: "For the first time in years I feel alive."
In this clip from the live TV special which was broadcast last summer, Cowan is seen laughing at Brendan O'Carroll's antics.