Kevin Sweeney resigned as department of defence chief of staff. Announcing his decision in a statement, the rear admiral said: "After two years in the Pentagon, I've decided the time is right to return to the private sector.”
Pointedly, he paid tribute to “the men and women of the department of defence” – but made no mention of Mr Trump.
The resignation comes days after James Mattis left his post as defence secretary. The four-star general announced his departure in December telling Mr Trump he believed in "treating allies with respect".
He added: "Because you have the right to have a secretary of defence whose views are better aligned with yours on these and other subjects, I believe it is right for me to step down from my position."
Department spokeswoman Dana White also left her post following the president's surprise announcement to leave Syria, as did Brett McGurk, the presidential special envoy to the global coalition fighting Isis.
Despite Mr Trump appearing to row back in the last week by suggesting the promised withdrawal would not be immediate, officials are said to have been astonished that he apparently took the decision without consultation after a phone call with Turkish president Recep Erdoğan.
It is understood Mr Erdoğan suggested the exit policy.
Withdrawal would leave America’s long term allies the Kurds vulnerable to manoeuvres by the Russian-backed Syrian army, as well as hostile Turkish forces.
Meanwhile, domestically, talks to end the partial shutdown of the federal government will resume on Sunday but a breakthrough looks unlikely after Mr Trump tweeted there was "not much headway made" in negotiations with Democrats after the latest meeting with his political rivals.
The Republican president has refused to fully fund the government until Congress grants $5.6bn for a US-Mexico border wall.
He has said he is prepared for the shutdown – which has left many workers without pay since December 22 – to last months or even years.
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