Russian Deputy Defence Minister Alexander Fomin said an American Poseidon-8 spy plane coordinated the attack on the Hmeymim air base in the south-east city of Latakia.
He also said the base was blasted by more than a dozen unmanned aircraft, according to TASS news agency.
Mr Fomin said the drones were not operated by some “sort of peasant, but a proper Poseidon-8 equipped with modern technology”, adding “it manually steered the drones”.
Reports of injuries from the assault are yet to be confirmed.
Mr Fomin also said the drones were destroyed by Russian air defences.
He added: “When these 13 drones faced our electronic warfare screen, they moved away to some distance, received the corresponding orders and began to be operated out of space.”
Mr Fomin also said the Kremlin is “receiving help in finding the so-called holes through which they started penetrating”.
Kremlin spokesman Dmitry Peskov refused to rule out whether Vladimir Putin would raise the alleged attack with Donald Trump before the two power leaders are expected to meet in Paris for a summit on November 11.
The news follows a chilling warning from US General Curtis Scaparrotti, who last week put Russia “on notice” during a rare interview suggesting America intensify its “war-capabilities” in case of an imminent attack.
General Scaparrotti has said that NATO is prepared for the “growing Russian threat” amid fears over escalating tensions between the two sides.
This came in the way of Russian President Vladimir Putin putting on a terrifying military drill, including a submarine carrying out a mock atomic missile strike.
Relationships between the US and Russia have taken a turn for the worse recently following allegations of cyberattacks and espionage.
Diplomatic relations between the two countries’ leaders have soured in recent months, with the Kremlin accused of interfering in the US Presidential election and dozens of Russian diplomats expelled from Washington following the Salisbury poisoning.
Russian President Vladimir Putin has since argued it is of the utmost importance for the two countries to start talks on nuclear disarmament before 2021.