McGurk's resignation, effective December 31, comes on the heels of Mattis's decision to quit the Trump administration over key disagreements with the US president, notably the Syria withdrawal.
|Brett McGurk (AP)|
Just last week McGurk, a Barack Obama appointee whom Trump kept on, said "nobody is declaring a mission accomplished" in the battle against IS -- just days before the president blindsided politicians and allies with his announcement of victory against the jihadist movement.
Trump on Saturday said that the jihadist group "is largely defeated."
"When I became President, ISIS was going wild," the president tweeted. "Now ISIS is largely defeated and other local countries, including Turkey, should be able to easily take care of whatever remains. We're coming home!"
Trump later took aim at McGurk on Twitter, referring to him as a "grandstander" who was quitting just before his time was up.
McGurk, 45, was set to leave his position in February, but reportedly felt he could no longer continue in the job after Trump's declaration and on Friday evening informed Secretary of State Mike Pompeo of his intention to wrap up at year's end.
His conclusion mirrored that of Mattis, who was seen as a voice of moderation in the mercurial Trump White House and quit after telling the president he could not go along with the Syria decision.
McGurk has served as the US envoy to the Global Coalition to Defeat ISIS, an acronym for the jihadist group, since 2015.
He also served as the deputy assistant secretary of state for Iraq and Iran, and worked under Republican George W. Bush as a senior official on Iraq and Afghanistan.
Discussing the US role in Syria this month, he had told journalists that "it would be reckless if we were just to say, 'Well, the physical caliphate is defeated, so we can just leave now.'"
"I think anyone who's looked at a conflict like this would agree with that."
- 'Complete reversal of policy' -
McGurk called Trump's move to leave Syria "a shock" and "a complete reversal of policy that was articulated to us," in an email announcing his decision to colleagues that was obtained by The New York Times.
"It left our coalition partners confused and our fighting partners bewildered," he said, according to the newspaper.
"I worked this week to help manage some of the fallout but -- as many of you heard in my meetings and phone calls -- I ultimately concluded that I could not carry out these new instructions and maintain my integrity."
Just after announcing his Syria decision, Trump again confounded international partners with plans to slash troop numbers in Afghanistan.
The momentous reversal of years of US foreign policy will leave the war-torn regions at risk of continued and potentially heightened bloodshed.
In typical fashion, Trump said Saturday that the media was treating him unfairly over the Syria withdrawal decision.
"If anybody but your favorite President, Donald J. Trump, announced that, after decimating ISIS in Syria, we were going to bring our troops back home (happy & healthy), that person would be the most popular hero in America," he tweeted.
"With me, hit hard instead by the Fake News Media. Crazy!"
The troop pullout will leave thousands of Kurdish fighters -- which the Pentagon spent years training and arming against IS -- vulnerable to Turkish attack.
On Saturday, a senior Kurdish official called on the United States to prevent a potential Turkish offensive against areas in northern Syria inhabited by Kurds, calling it America's "duty to prevent any attack and to put an end to Turkish threats."
The US has for years supported the Kurdish-led Syrian Democratic Forces (SDF) in the fight against IS in Syria.
Aldar Khalil, a key player in establishing Syria's semi-autonomous Kurdish region in 2013, said the US and its partners "must honor their commitments."
Heavyweight adviser Mattis -- a decorated Marine general who was often referred to as "the last adult in the room" -- made clear in his resignation letter that pulling out of Syria crossed the line.
The departures of Mattis and now McGurk follow those of national security advisor H.R. McMaster and White House chief of staff John Kelly -- leaving Trump, who has no political, diplomatic or military experience, increasingly alone. (AFP)