The 37-year-old departed by mutual consent after 12 years at the club, it was announced on Thursday.
The decision came after Mackintosh met with new executive chairman Garry Cook to discuss future strategy. "I would like to thank Alistair for his decade of service," Cook told the club's official website.
"He took us through a period of great change, particularly the move from Maine Road to our home here at the City of Manchester Stadium and goes with our best wishes for the future."