The fighter jets took off from western Iran and conducted air strikes in Aleppo, Idlib and Deir el-Zor provinces.
Russian jets based in Iran on Tuesday struck targets inside Syria, the Russian defence ministry said, after Moscow deployed aircraft to an Iranian air force base to widen its campaign in Syria.
The ministry said the strikes, by Tupolev-22M3 long-range bombers and Sukhoi-34 fighter bombers, were launched from the Hamadan airbase in western Iran.
It is thought to be the first time 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 ministry said the strikes had targeted the Islamic State of Iraq and the Levant (ISIL, also known as ISIS) and fighters affiliated with the group previously known as the al-Nusra Front in the Aleppo, Idlib and Deir el-Zor provinces.
Both groups have been designated as "terrorists" by the United Nations. Last month, al-Nusra Front changed its name to Jabhat Fateh al-Sham and said it had severed a relationship with al-Qaeda.
The United States said it was still assessing the extent of Russian-Iranian cooperation but described the new development as "unfortunate".
State Department spokesman Mark Toner said the US was looking into whether the move violated UN Security Council resolution 2231, which prohibits the supply, sale and transfer of combat aircraft to Iran.
"It’s unfortunate but not surprising," Toner told reporters. "It speaks to a continuation of a pattern we’ve seen of Russia continuing to carry out air strikes, now with Iran’s direct assistance, ... that predominantly target moderate Syrian opposition forces."
’A sizeable military presence’
Earlier on Tuesday, Russia’s state-backed Rossiya 24 channel 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 fighters in Syria from southern Russia, were too large to be accommodated at Russia’s airbase inside Syria.
The Tupolev-22M3 is "a fairly large, supersonic, long-range, strategic bomber. It needs a bigger air field than Russia already has in Syria. The previous sorties that this plane has been on have been flown from an airfield in southern Russia, but the problem with that is that it’s 2,000km away from the targets that its striking in Syria. This airfield in Iran is only 900km away," Al Jazeera’s Rory Challands, reporting from Moscow, said.
"The advantage in reducing flight-time, costs, and what the Russians say is the effectiveness of the strikes, makes this a pretty clear tactical decision to make."
The Iranian airbase near Hamadan, sometimes also called Hamedan, is located in north-west Iran and the Russian bombers would have to over fly Iraq to conduct strikes in Syria.
Russian military analyst Pavel Felgenhauer called Moscow’s transfer of heavy bomber planes to Iran a "major move".
"It’s not just Russian planes touching down in Iran. To establish an operational base, they’d have to move hundreds of servicemen as well. Thousands of tonnes of munitions, fuel, [and] other equipment to operate heavy bombers from an Iranian base. So this is actually Russia establishing a rather sizeable military presence inside Iran," he told Al Jazeera from Moscow.
Iraqi Prime Minister Haider al-Abadi said on Tuesday that Iraq, which lies between Iran and Syria, had granted Russia permission to use its air space, on the condition the planes use corridors along Iraq’s borders and refrain from flying over Iraqi cities.
Abadi told a press conference the same permission has been given to air forces of a separate U.S.-led coalition against Islamic State flying to Syria from Kuwait.
Russia also gave advance notice to the U.S.-led coalition battling Islamic State in Syria and Iraq, complying with the terms of a safety agreement meant to avoid an accidental clash in the skies, said U.S.
Army Colonel Christopher Garver, a Baghdad-based spokesman for the U.S-led coalition.
Separately on Tuesday, the New York-based Human Rights Watch accused Syrian government forces and their Russian allies of using incendiary weapons, which burn their victims and start fires, in rebel-held civilian areas of north and north-western Syria.
"Incendiary weapons have been used at least 18 times over the past six weeks, including attacks on the opposition-held areas in the cities of Aleppo and Idlib on August 7, 2016," the rights group said.
Photographs and videos recorded by Human Rights Watch at the time of the attacks indicated there were incendiary weapon attacks on opposition-held areas in the Aleppo and Idlib provinces between June 5 and August 10.
"Countries meeting at the Convention on Conventional Weapons (CCW) in Geneva on August 29 should condemn the use of air-dropped incendiary weapons ... and press Syria and Russia to immediately stop using incendiary weapons in civilian areas," HRW said.
Fighting in Aleppo intensified in early July when government forces captured the last supply route to the rebel-held eastern sector of the city, raising fears that its estimated 250,000 to 300,000 remaining residents could suffer a lengthy siege.