The strike was the second US operation in June to target a senior jihadist in Syria.
The US military said it carried out a "kinetic strike" targeting a leader of the Hurras al-Din jihadist group, an Al-Qaeda affiliate, in the Syrian province of Idlib on Monday.
"Abu Hamzah al Yemeni was traveling alone on a motorcycle at the time of the strike," US Central Command said in a statement, adding that an "initial review indicates no civilian casualties."
"The removal of this senior leader will disrupt Al-Qaeda's ability to carry out attacks against US citizens, our partners, and innocent civilians around the world," Central Command said.
The US is "highly confident" that the strike, carried out from a drone, killed Abu Hamzah al Yemeni, a US official with knowledge of the operation told CNN, speaking on condition of anonymity.
The strike was the second US operation in June to target a senior jihadist in Syria.
US forces captured Hani Ahmed Al-Kurdi, a leader of the Islamic State (IS) group, on June 16 during a raid in Aleppo province.
They also killed IS leader Abu Ibrahim al-Hashimi al-Qurashi during an operation in Atme, a region of Idlib province, on February 3.
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