A suicide bomber killed at least 20 people near Damascus' central square as authorities said they had prevented two other similar attacks aimed at crowds returning to school and work after a major Muslim holiday.
Three attackers had attempted to stage bombings using cars laden with explosives, Syrian authorities said.
One succeeded in blowing up his vehicle near the central Tahreer Square on Sunday morning, which was busy with commuters on the first full work day after the end of the Eid holidays. The Syrian working week runs from Sunday to Thursday.
Syria's foreign office said that 20 people, according to a report from state news agency SANA.
The two other cars were intercepted at checkpoints on the road near to the city's airport and later safely detonated in controlled explosions.
Syria's Minister of Local Administration, Hussein Makhlouf, said the response marked "a major success in foiling a plot".
Suicide attacks have been relatively rare in Damascus, a stronghold for President Bashar Assad as he battles rebel forces and Isis in a bloody and drawn-out war.
Pro-government forces have engaged in heavy fighting in Damascus' suburbs during the war, but have largely kept the rebels out of the city center.
In recent days, Syrian troops and allied forces have been fighting to drive the rebels out of AinTerma and Jobar, adjacent areas on the city's eastern outskirts that have been under rebel control since 2011.
The attacks come days before Russian-sponsored talks are to resume in the Kazakh capital, Astana.
Both sides have agreed to a cease-fire earlier this year during an earlier round of the talks, but it has been repeatedly violated.