Defence Secretary Chuck Hagel is stepping down after criticism of the campaigns in Afghanistan and against the Islamic State.
President Barack Obama is to announce the 68-year-old former senator and Vietnam war veteran’s departure later in the day in a statement from the White House.
The statement is expected at 11.10am local time (4.10pm UK time).
The news was first reported by The New York Times and then confirmed by administration officials.
Mr Hagel, a former Republican senator, has served as Pentagon chief since early 2013.
A senior defence official said Mr Hagel submitted his resignation letter to the President on Monday morning and that Mr Obama accepted it.
Both Mr Hagel and Mr Obama “determined that it was time for new leadership in the Pentagon”, the official said, after the two men held discussions over several weeks.
Mr Hagel agreed to remain in office until his successor is confirmed by the Senate.
Mr Hagel served as senator from Nebraska and became a critic of US involvement in Iraq. He received two Purple Hearts for his service in the Vietnam War.
Sky News US correspondent Dominic Waghorn said: “He has had outstanding differences with the close-knit team of advisors around the President, he’s never quite managed to break into that.
“And over the last few weeks and months there have been real points of disagreement between him and other officials in the Pentagon … on the issue of ISIS, on the issue of what to do in Syria in particular.”
Speculation had mounted in recent weeks over Mr Hagel’s fuure in the administration, and he himself addressed those rumours during an interview on the Charlie Rose show last week… see more