Military denies reports the aircraft had been carrying radioactive material when it came down near Glamis, just 35 km from the Mexican border.
A military aircraft has crashed in southern California, a spokesperson for the US Marines said.
There was no immediate word on casualties, but the military denied reports on Wednesday the aircraft had been carrying radioactive material when it came down near Glamis, just 35 kilometres from the Mexican border.
"We can confirm that an aircraft belonging to 3d Marine Aircraft Wing crashed near Glamis," a spokesperson told the AFP news agency.
"Military and civilian first responders are on site. Contrary to social media rumors, there was no nuclear material on board the aircraft."
The nearby Marine Corps Air Station Yuma is home to a number of MV-22 Ospreys.
The Osprey is a so-called "vertical takeoff and landing" aircraft that has rotary wings which can be directed upward to give it the maneuverability of a helicopter or forward to give it the range of a plane.
The US military has suffered a number of crashes with the aircraft, including an accident in Norway in March that left four Marines dead.