ISIS's exit from oil-rich Deir ez-Zor, which borders Iraq and is the main entry point to Syria for arms and fighters from Iraq, is the latest in a series of military defeats inflicted on the group in recent weeks .
The rout followed three days of violent clashes with the Al-Nusra Front and other rebel groups, the UK-based Syrian Observatory for Human Rights said.
In a message posted to jihadist websites on 3 February, Al-Qaeda disowned ISIS, which has has been locked in deadly clashes with other Syrian rebel groups since last May.
The clashes broke out after Al-Qaeda leader Ayman al-Zawahiri rejected an attempt by the group to merge with the terror network's official branch the Al-Nusra Front in Syria.
The move was also rejected by Al-Nusra leader Abu Mohammed al-Julani.
Besides attacking fellow rebels, including secular ones, ISIS's mainly foreign fighters have have also been condemned for abuses against civilian supporters of the opposition.
Iraq-based ISIS follows Al-Qaeda's hardline ideology and, until the 3 February disavowal, the two groups were widely believed to be linked.