Col Sonny Leggett said: "While the cause of crash is under investigation, there are no indications the crash was caused by enemy fire."
The aircraft crashed in Deh Yak district, Ghazni province, an area with a strong Taliban presence.
It is unclear how many people were on board.
Col Leggett denied Taliban claims that additional aircraft had crashed.
Taliban social media accounts have posted unverified footage showing a burnt-out plane with US Air Force markings.