Theron, 44, will be replaced by an actress in her 20s for the new Mad Max film. Video / Warner Bros.
International critics have voted Mad Max: Fury Road as their best film of the year, their main federation says.
Director George Miller's acclaimed action movie will be awarded the Grand Prix of the International Federation of Film Critics (FIPRESCI) at the San Sebastian film festival in Spain on September 18.
"You could have knocked me over with a feather! It's lovely to have this great cohort of critics acknowledge our collective labours in this way," Miller said in a statement.
The vote saw 493 of the world's top critics, who typically reward less mainstream arthouse films, choose from among movies premiered after July 1, 2014.
Mad Max: Fury Road, starring Tom Hardy and Charlize Theron - the fourth film in the apocalyptic adventure franchise - will receive a special screening at the festival, the highest-profile movie event in the Spanish-speaking world, which runs until September 26.
Last year's winner of the award was Richard Linklater for Boyhood.
The festival, held each year in San Sebastian, a picturesque seaside resort on Spain's northern Atlantic coast, was originally intended to honour Spanish language films but has established itself as one of the most important movie festivals in the world.
It hosted the world premiere of Alfred Hitchcock's spy thriller North by Northwest in 1959 and Woody Allen's Melinda and Melinda in 2004.
