The Syrian Democratic Forces (SDF), an alliance of Kurdish and Arab fighters, seized control of the only major road linking Raqa along the Euphrates valley to Deir Ezzor, the Syrian Observatory for Human Rights monitoring group said.
"The route... Linking Raqa to Deir Ezzor was cut this morning," an SDF commander confirmed.
The SDF launched its offensive for Raqa -- the de facto Syrian capital of IS's so-called caliphate -- in early November and has since seized swathes of territory in northern Syria from the jihadists.
Deir Ezzor province lies just east of Raqa and is almost completely held by IS. The jihadists also hold most of the provincial capital of the same name, and have been battling regime forces to overrun the city.
The SDF alliance, dominated by the Kurdish People's Protection Units (YPG), has benefitted from air support, equipment and training provided by the US-led coalition that has been carrying out air strikes against IS in Syria and neighbouring Iraq since 2014.