Islamic State jihadists captured the key Brigade 93 Syrian army base in Raqa province overnight, the Syrian Observatory for Human Rights said on Friday.
"The IS took Brigade 93 after fierce fighting and a triple suicide bomb attack," Observatory chief Rami Abdel Rahman said, adding that government forces now hold just one position in the province at Tabqa military airport.
He said IS fighters were now preparing to attack the airport, the last bastion in the province of President Bashar al-Assad's forces.
Since February, most of Raqa has been held by the Islamic State after the jihadists ousted mainstream rebel groups battling Assad's regime.
Some troops had already pulled out of Brigade 93 in July after IS captured Division 17, another base in the region where at least 85 people were killed in fighting or summarily executed shortly afterwards, the Britain-based Observatory said.
It said that in the fighting for Brigade 93, "36 soldiers were killed, some of whom were beheaded, while others died in the fighting or in the initial triple suicide bombing" that launched the attack.
At least 15 jihadists were killed, including the three suicide bombers who blew themselves up at the entrance to the base at the start of the attack on Wednesday night.
"Assad had pledged to retake Raqa. Not only has he failed to do so, he has lost his bases," Abdel Rahman said.
When he was sworn in for a third term, after an election denounced by the opposition and much of the international community as a sham, Assad vowed to free Raqa of "terrorists".
His regime uses the catch-all term to refer to all of those who oppose Assad's rule, political opposition and armed rebels alike.
Since joining the conflict in Syria in spring 2013, IS has seized control of almost all of Raqa and Deir Ezzor provinces on the border with Iraq, where it has waged a devastating offensive since June.
At the end of June, IS declared a caliphate in territory it controls in Syria and Iraq.
The Observatory estimates that more than 170,000 people have been killed in Syria since March 2011, the start of a peaceful uprising against Assad's regime that developed into an armed revolt.