US Defence Secretary Jim Mattis has resigned, saying his views are not aligned with President Donald Trump’s.
It comes a day after Mr Trump announced all US troops would be withdrawn from Syria despite opposition from allies and top military officials.
Mr Mattis will leave by the end of February after two tumultuous years struggling to soften and moderate the president's hardline and sometimes sharply changing policies.
He told Mr Trump in a letter that he was leaving because "you have a right to have a secretary of defence whose views are better aligned with yours".
Mr Trump tweeted that General Mattis "was a great help to me in getting allies and other countries to pay their share of military obligations".
He did not name a successor for Mr Mattis, but said one would be appointed shortly.
Mr Mattis, in his resignation letter, emphasised the importance of standing up for US allies.
"While the US remains the indispensable nation in the free world, we cannot protect our interests or serve that role effectively without maintaining strong alliances and showing respect to those allies," Mr Mattis wrote.
His departure has long been rumoured but officials close to him had insisted the battle-hardened, retired marine would hang on.
A White House official said Mr Mattis informed Mr Trump of his decision to leave the administration on Thursday afternoon.
Mr Mattis joins a long list of former Trump administration senior figures who have either quit or been removed.
Trump's White House has had the highest turnover of senior-level staff of the past five presidents, according to the Brookings Institution think tank.
