The actor – who has portrayed the titular character and his alter-ego Peter Parker for the past three movies – and the film’s director Sam Raimi won’t be returning after clashing with producers over the script.
Sam said: “While Tobey and I were looking forward to doing a fourth one together, the studio and Marvel have a unique opportunity to take the franchise in a new direction, and I know they will do a terrific job.”
Sony Pictures, who are making the movie, insist the project will still go ahead but will now be released in 2012, instead of next year as previously planned.
However, it is thought they will now make a prequel about Peter Parker as a teenager instead, meaning Kirsten Dunst – who played love interest Mary Jane Watson – will also not return.
Director Sam has previously suggested the franchise would be taking a more mature direction.
He said: “I’ve been talking with Tobey about where his character might grow to in this instalment. Parker started as a little bit of a selfish, naive and insecure high school kid … In the second picture, he wrestled with his personal fulfilment versus that responsibility and, in the third film, I think it was a little bit about his growing hubris.”