The official SANA news agency said two suicide bombers, one in a car, attacked the entrance to the Sayyida Zeinab shrine, which is revered by Shiites around the world.
The Syrian Observatory for Human Rights, a British-based monitoring group, said at least 20 people were killed, including 13 civilians, and more than 30 wounded in the blasts.
SANA gave a toll of at least 12 dead and 55 wounded.
IS claimed the attack via its Amaq news agency, saying it was carried out by three suicide bombers.
Syria's official Al-Ikhbariya channel showed images from the scene of burned-out cars billowing with plumes of black smoke.
Firefighters battled to extinguish the flames as shop signs lay in the street.
The last attack on Sayyida Zeinab on April 25 killed at least seven and wounded dozens.
A string of IS bombings near the shrine in February left 134 people dead, most of them civilians, according to the Observatory.
Lebanese Shiite militant group Hezbollah cited the threat to Sayyida Zeinab as a principal reason for its intervention in Syria's civil war on the side of President Bashar al-Assad.
The shrine contains the grave of Zeinab, a venerated granddaughter of the Prophet Mohammed, and is renowned for its glistening golden, onion-shaped dome.
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