The Boyzone singer has played Ciaran McCarthy on and off for nearly ten years and returns to the Street later this month to film a dramatic Christmas storyline.
Duffy has decided to leave Coronation Street permanently to spend more time with his wife Lisa and their children - 15-year-old Hollyoaks actor Jay and Mia, 11 - the Daily Star Sunday reports.
A source said: "Something had to give and sadly it was Corrie. He's had a great time working on the show but these last few months have proved very demanding.
"His daughter Mia, who has autism, is starting secondary school and it's a big year for Jay as he has his exams. So he's decided he wants to be at home in Dublin for them both."
The 36-year-old's character will be involved in a plot with on-screen girlfriend Michelle Connor, played by Kym Marsh.
A Coronation Street spokesman added: "It's going to be a very dramatic time for Ciaran."
> Keith Duffy praises son Jay: 'He's a natural on Hollyoaks'
> Kym Marsh ponders Coronation Street romance future