Tupolev-22M3 long-range bombers and Sukhoi-34 strike fighters took off from Hamedan on Wednesday, a statement said.
The aircraft attacked jihadist militants in Aleppo, Idlib and Deir al-Zour provinces, it added.
It is reportedly the first time Russia has struck targets inside Syria from a third country since it began a campaign to prop up Syria’s president last year.
Iran is Bashar al-Assad’s main regional ally and has provided significant military and financial support since an uprising against him erupted in 2011.
In recent months, senior Russian and Iranian officials have discussed boosting their military co-operation, reports the BBC’s Steve Rosenberg in Moscow.
Last week, Russia asked Iran and Iraq to allow Russian cruise missiles to fly through their airspace for attacks on terrorist targets in Syria.
Russia has been operating jets and helicopters from bases in Syria for the past year, but this is the first time that Moscow has deployed aircraft to a third country in the region.
Reports indicate that up to six Tupolev Tu-22M3 bombers – known by the NATO codename of “Backfire” – are now operating from an air base in western Iran.
These planes – originally designed as a long-range strategic bomber – have already been engaged in the Syrian air campaign but operating from bases in southern Russia. Placing them in Iran dramatically reduces the duration of their missions. The Russian defence ministry says that an unspecified number of Sukhoi-34 strike aircraft have also been sent to Iran.
Their deployment marks an intensification of the Russian air campaign – perhaps a reflection of the scale of the fighting in and around Aleppo – and it is a demonstration of the growing warmth in ties between Moscow and Tehran, the Syrian government’s two closest allies.
The Russian defence ministry statement said Wednesday’s air strikes had killed a “large number” of militants and resulted in the destruction of five large warehouses filled with weapons, ammunition and fuel, and jihadist training camps in the northern provinces of Aleppo and Idlib.
Three command centres in the eastern province of Deir al-Zour were also hit, it added.