Suicide bombings near a Shiite shrine outside Syria's capital and in Homs killed more than 150 people, as Washington and Moscow worked to secure a ceasefire.
At least four blasts struck the southern Damascus suburb of Sayyida Zeinab, killing at least 83 people, state media said, while earlier in Homs, 59 people, mainly civilians, were killed in a double car bombing, a monitoring group reported.
Two of the blasts near the Sayeda Zeinab shrine were caused by car bombs, while the remaining two were suicide bombers, Reuters reported citing pro-government media.
The monitoring group the Syrian Observatory for Human Rights also said among those killed were students leaving a school.
Isis claimed responsibility for the attack through its al-Amaq news agency, said Michael Horowitz, a security analyst for the Levantine Group.
The blasts came hours after twin suicide attacks in the city of Homs. Syria's official news agency SANA, quoting a police source, said 178 people, including children, were among the wounded.
Meanwhile, US Secretary of State John Kerry has said a "provisional agreement" has been reached with Russia on a partial truce in the conflict and spoke optimistically about progress towards a possible ceasefire.
He had spoken to his Russian counterpart Sergei Lavrov, he said, and they had agreed on terms but details still needed to be worked out.
Syrian President Bashar al-Assad, meanwhile, told Spain's El Pais newspaper he was "ready" for a ceasefire, but that it should not be exploited by "terrorists".