The explosion that killed Damascus Mufti Mohammed Adnan Afiouni took place in the town of Qudsaya, west of the capital of Damascus. It was not known who planted the roadside bomb and no group immediately claimed responsibility for the attack.
The cleric was first reported wounded and then declared dead soon after.
Syria's ministry of religious endowment, or Awqaf, announced Afiouni's death, calling it a terrorist act. Damascus and its suburbs have largely been free of violence or attacks as the government tightened its control of the area, expelling rebel fighters.
Afiouni had been a key figure in the government's so-called reconciliation deals with rebels and opposition-held areas.
He was one of the mediators of the 2016 deal under which rebel fighters in Daraya, a key town in Damascus suburbs, surrendered after a four-year grueling siege and military campaign. The rebel fighters and remaining residents were evacuated to the northwestern province of Idlib and government forces entered the destroyed town in 2016.
After the evacuation, Afiouni led prayers in the town, attended by Syrian President Bashar Assad.
Daraya was one of the first towns to stage a protest against Assad's government in 2011. The protests were met with a violent government crackdown, and the crisis eventually descended into a full-blown civil war that has devastated Syria and left millions homeless, displaced, imprisoned or dead.
Assad described his opponents, including those who carried arms, as terrorists and empowered Islamic clerics and the ministry of Awqaf to play a key role in combatting extremism. Assad appointed Afiouni in 2019 to head the newly-founded Islamic al-Sham Center to combat terrorism.
At the time, Afiouni said the center — which was to teach and train Islamic clerics while aiming to also host international scholars — would play a role to reform extremist ideas spread during the years of the conflict.