Sean Bailey's billion-dollar blockbusters included The Lion King, Beauty and the Beast and Aladdin
The move will see motion picture production president Sean Bailey stepping down after a decade and a half in the role.
He will be replaced by David Greenbaum, head of Disney's Searchlight Pictures.
It follows recent disappointing box office performances, including Haunted Mansion and Jungle Cruise.
Disney said Mr Bailey will stay at the company as a producer on the upcoming science fiction movie Tron: Ares and other projects.
During his tenure, Mr Bailey oversaw live-action adaptations of Alice in Wonderland, Maleficent and, The Jungle Book.
His blockbuster movies also included The Lion King, Beauty and the Beast and Aladdin.
Together his productions brought in an estimated $7bn (£5.5bn) in global box office takings for the media giant.
But last year, he was also responsible for The Little Mermaid which failed to achieve the success of others.
"Sean has been an incredibly important member of the Studio's creative team for well over a decade," said Disney Entertainment Co-Chairman Alan Bergman.
"He and his team have brought to the screen iconic stories and moments that have delighted fans around the world and will stand the test of time."
Mr Greenbaum has been appointed to the newly-created role of president at Disney Live Action and 20th Century Studios.
He was involved in the movie Poor Things, which has gained 11 nominations including best picture, for this year's Oscars.
Disney has been under pressure from activist investor Nelson Peltz, who has called for a shakeup of the business.
The US billionaire wants Disney to boost profits from its streaming business as well as improve the box office performance of its films.
Mr Peltz has repeatedly demanded a seat on Disney's board. On Monday, the firm sent a letter to shareholders urging them not to support his bid to become a board member.
Earlier this month, Mr Iger, announced a series of moves which he hopes will bring "significant growth" to the entertainment giant.
The plans include streaming an exclusive version of Taylor Swift's Eras Tour concert movie on Disney+.
The firm will also invest $1.5bn (£1.2bn) in Epic Games, the maker of the hugely popular video game Fortnite.
A day before that announcement, Disney also unveiled a joint venture with rivals Fox and Warner Bros. Discovery to launch a new sports streaming platform.
Together, the three US media giants own a wide range of sports rights including the FIFA World Cup, Formula 1, National Football League, National Basketball Association and Major League Baseball.
Mr Iger previously headed Disney for 15 years before retiring at the end of 2021 but made a shock return to the firm less than a year after stepping down.
He was brought back after the company's share price plummeted and Disney+ continued to make a loss.
-- Courtesy of BBC News