McGurk submitted his resignation on Friday, a US State Department official said on Saturday, adding that the resignation will be effective on Dec. 31.
A person familiar with the matter said McGurk has quit because he is strongly opposed to Trump's troops withdrawal from Syria, Presstv Reported.
Trump announced his decision to withdraw some 2,000 US troops from Syria on Wednesday, asserting that Daesh (ISIL) Takfiri terrorist group had been defeated.
After Trump announced that Daesh had been defeated and US troops would withdraw from the Arab country, US Defense Secretary Jim Mattis also offered his resignation.
Both the Pentagon and the State Department were reported to be against the troop withdrawal.
Previously McGurk had once more opposed Trump on the issue of troop withdrawal from Syria.
Speaking back in April alongside a top Pentagon official, McGurk had said that US troops needed to stay in Syria until their mission was accomplished completely.
The comments were made just after Trump said that US troops would soon pull out of Syria.
McGurk's departure follows the abrupt resignation of Defense Secretary Jim Mattis, who was also opposed o the withdrawal of troops from Syria and reducing the US presence in Afghanistan.
Mattis wrote in his resignation that he and the president did not see eye to eye, adding that it was the president of the United States right to choose a defense secretary whose views were “better aligned” with the views of the Commander in Chief. However, both Republican and Democratic lawmakers have voiced deep concern over his resignation.