The 58-year-old, who plays café-owner Roy Cropper in the show, will take time off at the same time as his on-screen wife Hayley (Julie Hesmondhalgh).
During his two-month break Neilson will star as Lucky in Samuel Beckett play Waiting For Godot in Manchester from February 1 to March 8 next year.
Roy will be seen leaving the show with Hayley when they decide to do voluntary work with disadvantaged children in Africa, and Becky Grainger (Katherine Kelly) will keep the café open in his absence.
Corrie bosses have insisted that it is only temporary and Neilson has not quit the show. A spokesperson said: "David will be treading the boards for a while but he remains firmly with the show.
"He will only be off screen for a couple of weeks but away from us for a couple of months."
Neilson added: "The last time I was on stage was 13 years ago and I’m interested in being in a rehearsal room again for three or four weeks.
"It’s going to be a bit of a culture shock, not least having to turn up for a second night to do it, because usually once I’ve done it I go home.
"The offer came totally out of the blue."
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