The actor, who voices Mr Burns, Ned Flanders, Principal Skinner and Waylon Smithers, tweeted the news, saying his contract had not been renewed with Fox.
He wrote: “From James L. Brooks’ lawyer: show will go on, Harry will not be part of it, wish him the best.
“This because I wanted what we’ve always had: the freedom to do other work.
“Of course, I wish him the very best.”
A few hours later he posted again on the social media site: “Thanks, Simpsons fans, for your support.”
20th Century Fox, which produces the show, has not released an official comment.