The men were assassinated Tuesday evening as they left a meeting in al-Zabadani where they had discussed the area's national reconciliation efforts, the Fars news agency reported Wednesday.
Majed Tinawi, the city's mayor, and Ghassan al-Haj Hammoud, a member of the National Reconciliation Committee, died immediately, police said.
The deaths were part of ongoing violence across Syria.
A total of 134 people, including 30 children, were killed Tuesday in shelling by government forces, the Syrian Network for Human Rights reported.
An entire family of three adults and four children died when shells hit the village of Ter Maali, the pro-rebels group said.
Six girls and four women died when shells hit the Hamza Ben Abdulmotalelb mosque in Aleppo, the group said.
The network's casualty figures are not confirmed.