The ministry said the strikes, by Tupolev-22M3 long-range bombers and Sukhoi-34 fighter bombers, were launched from Iran’s Hamadan air base.
It is thought to be the first time that Russia has struck targets inside Syria from Iran since it launched a bombing campaign to support Syrian President Bashar al-Assad in September last year.
The move shows Russia is expanding its role and presence in the Middle East and comes amid Russian media reports Moscow has asked Iran and Iraq for permission to fire cruise missiles at Syrian targets across their territory from the Caspian Sea.
The ministry said Tuesday’s strikes had targeted Islamic State and militants previously known as the Nusra Front in the Aleppo, Idlib and Deir al Zour provinces.
The bombers had been protected by fighters based at Russia’s Hmeymim air base in Syria’s Latakia Province, it said.
Russia’s state-backed Rossiya 24 channel earlier on Tuesday broadcast uncaptioned images of at least three bombers and a Russian military transport plane apparently inside Iran, but said it was unclear how many Russian bombers had arrived there.
It said the deployment would allow the Russian air force to cut flight times by 60 percent and increase bombing payloads.
Russian media said the Tupolev-22M3 bombers, which had already conducted many strikes on militants in Syria from their home bases in southern Russia, were too large to be accommodated at Russia’s air base inside Syria.
The Iranian air base near Hamadan, sometimes also called Hamedan, is located in north-west Iran and the Russian bombers would have to over fly Iraq to strike Syria.