The soldiers were part of the 2nd Armored Brigade Combat team and were heading from Fort Riley, Kansas to Poland to assist NATO troops.
Atlas Air Flight 5Y8380 originated in Topeka, Kansas and was on its way to Poland when it was diverted to O'Hare.
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A spokesperson for Atlas Air, which has a contract with the U.S. military, said there was "an indication of a potential abnormality in the cargo compartment soon after departure."
The plane landed safely just before 4 p.m. The Chicago Fire Dept. said 300 soldiers on board deplaned and were seen climbing onto waiting buses with a huge emergency police and fire response.
"As a precautionary measure, Chicago authorities inspected the aircraft upon arrival and determined the aircraft was safe for all passengers to de-plane," Atlas said in a written statement. "Our team is investigating the cause of this incident and will work to safely return the aircraft to service."
The Chicago Fire Department said more than 300 people were on board the plane.
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There are no reports of any injuries.