Stuart Murray, who has been president and chief executive officer of the national museum since 2009, is to end his term Nov. 2.
Chairman Eric Hughes says Murray oversaw the planning, construction and opening last month of the new museum, and has left it well positioned for the future.
The museum is the brain child of the late media magnate Izzy Asper and took more than a decade to build.
The facility ran into delays and cost overruns, and ended up costing $351 million.
It's not clear what lies ahead for Murray, who once served as leader of the Manitoba Progressive Conservatives.