Civilians and military personnel were killed in the attack on the military academy in the central province of Homs, Syria's defence ministry said in a statement, adding "terrorist" groups had used drones to carry it out.
The statement did not specify an organisation and no group immediately claimed responsibility for the attack.
Syria's defence minister attended the graduation ceremony but left minutes before the attack, according to a Syrian security source and a security source in the regional alliance backing the Damascus government against opposition groups.
"After the ceremony, people went down to the courtyard and the explosives hit. We don't know where it came from, and corpses littered the ground," said a Syrian man who had helped set up decorations at the academy for the occasion.
The Observatory said at least 78 people had been killed and more than 140 wounded. The source in the alliance backing Syria's government said the toll was at 66.
Syria's conflict began with protests against President Bashar al-Assad in 2011 but spiralled into an all-out war that has left hundreds of thousands dead and millions displaced.
The Syrian army has been gutted by the fighting, and relied heavily on military support from Russia and Iran as well as Tehran-backed fighters from Lebanon, Iraq and other countries.
Assad regained most of the country, but a swathe in the north bordering Turkey is still held by armed opposition groups, including hardline jihadist fighters.
(Reporting by Laila Bassam, Suleiman Al-Khalidi, Kinda Makieh and Maya Gebeily; editing by Jon Boyle, Mark Heinrich and David Gregorio)
