Hunnam had previously signed on to play wealthy young businessman Christian Grey alongside Dakota Johnson's inexperienced Anastasia Steele.
"The filmmakers of 'Fifty Shades of Grey' and Charlie Hunnam have agreed to find another male lead given Hunnam's immersive TV schedule which is not allowing him time to adequately prepare for the role of Christian Grey," the studios said Saturday in a joint statement.
Hunnam's casting was met with mixed reception. Some "Fifty Shades" mega-fans launched online petitions calling for the film's producers to replace him.
Sources told The Hollywood Reporter's Matthew Belloni that the 33-year-old actor "got cold feet" about the role.
"2 sources now say Hunnam got cold feet on #50Shades movie, TV schedule said to have had nothing to do with his exit," Belloni tweeted.
"Fifty Shades" author E.L. James responded to the shake up in a short but friendly statement.
"I wish Charlie all the best. x," she tweeted Saturday.