There were no survivors from the crash, which happened in a remote area near the village of Russian Mission.
Those killed included three people on a Cessna from Hageland Aviation, a local airline, and two on a Piper operated by Renfro's Alaskan Adventures, a tourism company, Alaska's national guard said.
Mid-air collisions are rare in the US and most occur near airports.
Five people have died in a mid-air collision between two small commercial planes in the US state of Alaska.