The shock attack comes despite a Russian air campaign targeting the group that began in September, and more than a year of strikes by a US-led coalition against the jihadists in Syria.
The Britain-based Syrian Observatory for Human Rights said IS had killed at least 135 people in the multi-front attack that began on Saturday.
The dead included 85 civilians and 50 regime fighters, according to the monitor, which said Sunday that IS had also kidnapped more than 400 civilians from captured territory.
“Those abducted, all of whom are Sunnis, include women, children and family members of pro-regime fighters,” Observatory chief Rami Abdel Rahman said.
He said they had been taken to areas under IS control in the west of Deir Ezzor province and to the border with Raqa province — the main IS stronghold in Syria — to the northwest.
The monitor said at least 42 IS fighters had been killed in the attack, adding that fighting was ongoing on Sunday, with regime forces backed by Russian air strikes trying to recapture lost ground.
Syria’s state news agency SANA said at least 300 civilians, “most of them women, children and elderly people,” had been killed in the assault.
It denounced the deaths as a “massacre”.