Syrian rebels, including jihadists, seized the last government-held town on the main highway between second city Aleppo and the city of Hama to its south on Thursday, a monitoring group said.
The blow to the Damascus regime came just a day after it recaptured from Islamic State terror forces an alternative route further east that had provided its sole link to neighborhoods of Aleppo under its control.
Jihadist faction "Jund al-Aqsa and opposition groups have seized full control of the town of Morek after a fierce offensive," the Syrian Observatory for Human Rights said.
The Britain-based watchdog's director Rami Abdel Rahman said that clashes were still raging in the south and east of the town, and that "dozens" of soldiers had been killed or wounded.
Jund al-Aqsa boasted of victory on its Twitter account, but a Syrian security source denied any major setback.
"There are clashes around Morek and there is some infiltration but the fighting is ongoing and we are dealing with the situation," he told AFP.
Morek has changed hands several times in Syria's four-year civil war. Government troops last retook it in October 2014.
Last month, Syrian troops launched a major fightback in Hama province with Russian air support, with the main Aleppo highway a principal objective.
It was one of a number of counteroffensives the Damascus regime has launched since Moscow intervened in its support on September 30. But they have faced fierce resistance, particularly in Hama.
"Instead of gaining ground, the regime has lost territory," Abdel Rahman said.
On Wednesday, the Syrian army recaptured the alternative route it was using to reach the government-held western sector of Aleppo city, relieving tens of thousands of stranded civilians.
Advancing ISIS forces had severed the road late last month.
AFP contributed to this report.