"The toll from the attacks increased to at least 221 dead, 127 of them civilians," Rami Abdel Rahman, of the Britain-based Syrian Observatory for Human Rights, told AFP.
The series of suicide bombings included a motorcycle bomber who struck at a busy vegetable market.
The coordinated attacks - the worst in recent months - had all the hallmarks of the Daesh group and were reminiscent of its horrific assaults that spread mayhem over the past years in Syria, already ravaged by civil war.
The bombings in the city of Sweida, a provincial capital populated by Syria's minority Druze, were apparently timed to coincide with attacks by a militant group linked to Daesh on a number of villages in the province, also called Sweida.
Al Ikhbariya state-run TV showed images from several locations in the province and its capital where the bombers blew themselves up. The breakdown of the fatalities from the attacks was not immediately known and no group immediately claimed responsibility for the bombings.
The rare attacks in Sweida came amid a government offensive elsewhere in the country's south. Government forces are battling the group near the frontier with Israeli-occupied Golan Heights and near the border with Jordan. The group also has a small presence on the eastern edge of Sweida province.
Daesh has been largely defeated in Syria and Iraq, but still has pockets of territory it controls in eastern Syria and in the country's south.
Since their offensive in June, Syrian President Bashar Assad's forces have retaken territories controlled by the rebels along the Golan Heights frontier and are now fighting militants in the country's southern tip.
The death toll, initially reported at 38, quickly climbed. The Britain-based Syrian Observatory for Human Rights also reported a series of suicide blasts in the city of Sweida and the clashes in the province's countryside.
The Observatory said the attacks killed a 100, including 28 pro-government fighters, four attackers and 12 militants. The discrepancy in death tolls is common in the early hours of such large attacks.
An activist-operated media platform on Facebook, Sweida News Network said a local militia was fighting the advancing of Deash group and that at least 30 militiamen were killed in clashes with the militants.
Al-Ikhbariya said one of the attackers hit at a vegetable market in the city of Sweida just after 5 a.m., a busy time for the merchants at the start of their day.
The bomber drove through the market on a motorcycle and there detonated his explosives, the TV station said. A second attacker hit in another busy square in the city. Two other attackers blew themselves up as they were chased by security forces, the TV said.
The city of Sweida has largely been spared most of the violence that Syrian cities have witnessed in the years since the conflict started in 2011.
