The 23-year-old – who has played troubled Craig Dean in the Channel 4 soap for five years – will bow out of the show next month when the John Paul-Craig-Sarah love triangle reaches its dramatic climax.
Producer Bryan Kirkwood told DS: "I am genuinely gutted that Guy is leaving the show, but after five years he feels the time is right. He's an amazing actor and has really come into his own through his work on the Craig and John Paul storyline - and has helped turn it into one of Hollyoaks' biggest ever storylines.
"We've left the door open for him to return and I wish him the very best of luck for whatever he does next."
He added: "I'd also like to thank all our fans on Digital Spy for their enthusiastic response for the McDean storyline. I hope they remain glued to the screen as the story moves into its final stage."
A show source said: "Craig is still unsure whether his feelings are for John Paul or Sarah, and so makes a makes a drastic decision to leave Hollyoaks after an explosive outing of his affair. Will Craig leave with John Paul's blessing? Or will John Paul put up a fight?"
Guy filmed his final scenes on Wednesday and will remain on screen until mid September.