The soldier, who has not been named, died after the device detonated in Ayn Issa, north of the IS stronghold Raqqa.
It is the first such death since US special forces deployed in Syria in October 2015.
Meanwhile at least 32 people have been killed in intense Syrian air strikes on rebel-held east Aleppo, monitors say.
The UK-based Syrian Observatory for Human Rights, which monitors casualties, said the attack was one of the heaviest since Syrian forces resumed an offensive on the east earlier this month.
A statement from the anti-IS US-led coalition said the serviceman died on Thursday from wounds sustained in the blast.
Coalition commander Lt Gen Stephen Townsend called the soldier a "hero" and praised those he said were protecting his country from IS's "hateful and brutal ideology".
"On this Thanksgiving, please be thankful that there are service members willing to take up the fight to protect our homeland," he said.
US Defence Secretary Ash Carter said the soldier's death was a "painful reminder of the dangers our men and women in uniform face around the world to keep us safe".
About 300 US special forces personnel have been deployed in Syria to advise an anti-IS alliance of Arab, Kurdish and other fighters, and improve the coalition's targeting of air strikes.
Meanwhile, the Syrian government has intensified its offensive on east Aleppo, monitors and activists say.
"There was an escalation in the evening, with successive bombardments," SOHR director Rami Abdel Rahman told AFP news agency, adding that many people were trapped under rubble.
Five children were reported to be among the dead.
Syrian forces stepped up ground and air attacks on eastern Aleppo in November following a three-week moratorium.
Once Syria's commercial and industrial hub, Aleppo has been divided roughly in two since 2012, with the government controlling the west and rebels the east.
In late September, two weeks after encircling the east and reimposing a siege on its estimated 275,000 residents, the army launched an all-out assault to take full control of the city.
Rebels launched a counter-attack in an attempt to break the siege in late October. But their progress slowed after early gains.
A US serviceman has been killed by an improvised explosive device while fighting against so-called Islamic State (IS) in Syria, officials say.