The separate car bomb and suicide attacks happened in Homs and southern Damascus, Syrian state media reported, citing local officials and security sources.
The deadliest attacks were on the southern outskirts of Damascus, where three bombers struck in the Sayyidah Zaynab district.
The blasts detonated near the revered "Lady Zeynab" Shia Muslim shrine, SANA reported. At least 83 were killed and 178 others injured there, according to SANA, citing its reporter on the scene and local sources.
Thirty-nine people were killed when two car bomb explosions struck a pro-regime neighborhood in central Homs, SANA reported.
The London-based monitoring group Syrian Observatory for Human Rights gave the death toll as 46, with more than 100 people wounded.
The observatory reported that the Damascus attacks were carried out via a suicide car bomb and by two suicide bombers.
ISIS claimed responsibility for the Sayyidah Zaynab and Homs attacks via the Telegram messaging app.
The U.N. Special Envoy for Syria, Staffan de Mistura, condemned the attack, saying that children were among the victims.
Alawite neighborhood targeted in Homs
Homs Gov. Talal al-Barazi told SANA that two cars packed with "huge amounts of explosives" were detonated near a bus stop in central Homs in the first attacks Sunday.
The blasts targeted students and government employees heading to work, the state-run TV station al Ikhbaria reported.
Images from the site of the blast showed dozens of destroyed vehicles and severe damage to nearby buildings.
The bombings took place in the al-Zahraa district, a regime-controlled neighborhood that is predominantly home to members of Syrian President Bashar al-Assad's Alawite sect.
Al-Barazi said the attacks were aimed at the support base of the Syrian government, as the country's army made gains against rebels around the country.
Fourth bombing in neighborhood since December
The Homs neighborhood has been struck by three similar bombings in the past three months.
At least 24 people were killed and 100 injured in a coordinated car bombing and suicide bombing on January 26. Twin bombings also struck the neighborhood on December 28 and December 12.
ISIS claimed responsibility for all three previous attacks.
Kerry: 'Closer to a ceasefire' than ever
Violence has continued to rage in recent days
in spite of hopes to implement a "cessation of hostilities." More than a dozen countries agreed to the ceasefire at talks in Munich, Germany
, earlier this month, but the agreement seems to have had little impact on the ground.
But at a press conference in Jordan on Sunday, U.S. Secretary of State John Kerry said a ceasefire was still "possible."
"We are closer to a ceasefire today than we have been, and I take nothing for granted about this," he told reporters at a joint press conference with Jordanian Foreign Minister Nasser Judeh.
Kerry had a telephone conversation with Russian Foreign Minister Sergey Lavrov on Sunday in which they "continued to discuss the modalities" of the truce, Russian state news agency Sputnik reported, citing the Russian Foreign Ministry.
More than 250,000 people have been killed, more than 1 million injured, and more than half of Syrians displaced since the country's civil war began in 2011, according to the United Nations.