Four distinct explosions were heard emanating from the base on Monday evening, Sputnik quoted locals as saying. Plumes of smoke could be seen rising from the facility.
Several drones were launched from the US base immediately after the attack.
The amount of damage to the base or casualties caused by the attacks are unknown, as the US has not yet commented on the incident.
The attack came after an attack in the nearby town of Al-Busayrah earlier on Monday, which was variously reported to have been carried out by American troops or the so-called Syrian Democratic Forces (SDF), a group of US-backed Kurdish militias who formally control the region in the absence of Syrian government authority.
According to reports by Syrian Arab News Agency (SANA), US troops raided the village at dawn, firing indiscriminately into several homes and killing at least four people, the London-based Syrian Observatory for Human Rights said. They also kidnapped several people and took them to an unknown location.