The crossover event will bring about continuity changes to the Marvel Universe, but the iconic character will not survive to feature in the Marvel NOW! era that follows.
"I got a little teary-eyed when we were scoping out the moment in the room with the series' writers and editors," Marvel editor in chief Axel Alonso told New York Daily News.
"He needed to be the casualty in this story. There's no more oh-sh-moment that you can bring than having a son killing his father."
Created by Stan Lee and Jack Kirby in 1963, Professor Xavier has been a key part of X-Men since the series debuted, and has been portrayed on screen by Patrick Stewart and James McAvoy.
"He was this thing that was just floating around the X-books, with not the same amount of gravitas that he once had," writer Brian Bendis added. "I did point out that he would matter more in death."
Marvel executive editor Tom Brevoort promised that Professor X's death will be "serious and lasting", unlike many other comic book fatalities.
Avengers vs X-Men #11 arrives in stores today (September 12).