Four of the six crew members were previously reported dead in the crash, which occurred in western Iraq on Thursday.
"The circumstances are being investigated," CENTCOM said.
Another American plane was involved in the incident but was able to land despite damage. The US says there was no shelling. However, Iran claims that groups allied with the Tehran regime shot it down.
The aircraft, a KC-135 Stratotanker, is used to refuel other aircraft in mid-air.
The US fleet of KC-135s is aging and is being gradually phased out in favor of more modern aircraft.
The last of these aircraft were manufactured in the 1960s, Yang Uk, a security expert at South Korea's Asan Institute for Policy Studies, told the AP.
This is the fourth US military aircraft lost in the ongoing war. Previously, three F-15E fighter jets were accidentally shot down over Kuwait. In those cases, everyone on board survived.
