US Central Command said the blast occurred near the former militant stronghold of Ayn Issa, but gave no other details, adding it would release more information "as appropriate".
The unnamed man died of his wounds on Thursday. Ash Carter, the outgoing US Defence Secretary, called the death a “painful reminder of the dangers our men and women in uniform face around the world to keep us safe".
Isis militants have been laying mines and booby traps throughout their former strongholds as the group is pushed back from swathes of territory it seized during a lightning advance through Iraq and Syria in 2014.
Kurdish Peshmerga forces uncovered bombs concealed within teddy bears and toy cars in one of the terrorists' former strongholds in Iraq and the explosives continue to pose a huge risk for civilians and soldiers alike.
There are believed to be around 300 US military personnel working in Syria, assisting and advising Syrian Kurdish and Arab rebel forces fighting Isis, ABC News reports.
Lieutenant General Stephen J Townsend, the commander of US-led coalition, offered his condolences to the killed soldier.
He said: "The entire counter-Isil (Isis) Coalition sends our condolences to this hero's family, friends and teammate.
"On this Thanksgiving, please be thankful that there are service members willing to take up the fight to protect our homeland from Isil's hateful and brutal ideology."
Last month, a US Naval officer was killed in Iraq near the city of Mosul in a roadside bomb while working as an adviser to Iraqi troops.
In October last year, President Obama ordered special forces to be deployed to Syria to aid and advise domestic opposition to Isis.
Americans have also volunteered to fight for rebel groups on the ground, including William Savage, Levi Jonathan Shirley and Jordan McTaggart, who died in battles with the People's Protection Units (YPG) near Manbij in July.
A British man, Dean Carl Evans, was also killed fighting for the YPG to retake the strategic city from Isis.Reuse content