The launch of surface-to-surface, medium-range missiles into Syria's Deir el-Zour province comes as Islamic State militants fleeing a US-led coalition onslaught increasingly try to fortify their positions there.
Activists in Syria said they had no immediate information on damage or casualties from the strikes, launched from Iran's Kurdistan and Kermanshah provinces.
Social media was awash in shaky mobile phone footage from those areas, allegedly showing the missiles rise in an orange glow before heading toward their targets.
Iran's Revolutionary Guard, a hard-line paramilitary force, has seen advisers and fighters killed in the conflict.
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A Guard statement carried on its website said many "terrorists" were killed and their weapons had been destroyed in the strike. It described targeting a command center and an area used to build suicide car bombs in the provincial capital, also named Deir el-Zour.
"The message of the revolutionary and punishing move is totally clear," the Guard said in its statement, carried by the state-run IRNA news agency.
Iran's semi-official Fars news agency, believed to be close to the Guard, said the paramilitary force launched a total of six missiles that flew over Iraqi airspace before striking Syria.
Deir el-Zour is home to both Islamic State militants and civilians. The extremists increasingly have fled to Deir el- Zour as the Islamic State group's de facto capital of Raqqa has come under punishing US-led airstrikes.
Five Islamic State-linked attackers stormed Iran's parliament and a shrine to revolutionary leader Ayatollah Ruhollah Khomeini on June 7, killing at least 18 people and wounding more than 50.
Iran has described the attackers as being "long affiliated with the Wahhabi," an ultraconservative form of Sunni Islam practiced in Saudi Arabia. However, it stopped short of directly blaming the kingdom for the attack, though many in the country expressed suspicion Iran's regional rival had a hand in the attack.