The strike on the town of al-Bab, northeast of the city of Aleppo, used barrel bombs - steel drums full of shrapnel and explosives, the Syrian Observatory for Human Rights said.
Syrian President Bashar al-Assad has denied the air force uses such devices.
Dozens of people were wounded in the attack as well as the at least 59 killed, according to the monitoring group, which gathers information from sources on the ground. The town has been the focus of several heavy bombardments by the military since late last year
A second Syrian air force raid in a rebel-held part of Aleppo city killed at least 12 civilians on Saturday, the Observatory said.
State news agency SANA did not report on these specific raids but, citing a military source, said the armed forces had targeted Islamic State in Aleppo province's eastern countryside and hit insurgents on a road running north to the border with Turkey, as well as to the south of Aleppo city and within the city itself.
The military has been hit by a series of recent setbacks. Insurgents, including al Qaeda's Syrian wing Nusra Front, celebrated inside the last government-held town in Idlib province on Friday after capturing it the night before while Islamic State has secured its grip on the ancient central city of Palmyra.
In Syria's northeast, clashes erupted between the military backed by allied militias and Islamic State to the south and southeast of Hasaka city, the Observatory said on Friday, after the al Qaeda offshoot planted a bomb on the edge of the city.
The Observatory said the blast killed a number of pro-government fighters while at least 10 died in the subsequent clashes. An Islamic State statement posted online described the blast as a suicide attack and said it had killed more than 30 of its opponents.
Hasaka province lies next to Islamic State-held territory in Iraq, where the group is back on the offensive after losing the city of Tikrit at the start of the month.
SANA said the Syrian military had foiled an attack on Hasaka and had killed dozens of militants in the province. It said it had been targeting Islamic State in the provincial countryside with the help of Kurdish YPG militia. The YPG, which has fought the fiercest battles against Islamic State in the northeast, says it does not coordinate with the Syrian military.
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