Explosions and gunfire shook the area around the Ummayad mosque on Tuesday, as rebels battled troops on the grounds of a police academy elsewhere in the province, the Syrian Observatory for Human Rights said.
A military source also reported heavy fighting and said rebels had detonated an explosive near the southern outer wall of the mosque in an attempt to break into the courtyard.
The army has full control of the mosque itself, but rebels hold positions around the southern entrance.
In October, the mosque was heavily damaged when a fire broke out amid clashes and charred several antique furnishings and one of its intricately sculpted colonnades. At the time, thieves stole three hairs and part of a tooth said to have been from the Muslim Prophet Mohammed that were among the mosque's most renowned, an AFP reporter learned.
The site has been a place of Muslim worship since the 8th century, but the original building was razed by the Mongols in the 13th century, from when the current structure dates.
Today it is again in danger, as fighting has raged in Aleppo since mid-July, including in its UNESCO-listed Old City which embraces the ancient citadel and historic covered market and the mosque.
Elsewhere in Aleppo province, rebels pushed into the grounds of a major police academy and seized one of its buildings after a fierce two-day siege in which more than 70 combatants were killed, the Observatory said.
The academy, located near the town of Khan Assal, is one of the last regime bastions in the province.
A second military source said that rebels were blockading the entrance of the school and that clashes were continuing on the periphery. "We called for reinforcements yesterday and they have still not arrived," he told AFP on condition of anonymity.
Regime forces retaliated with air strikes on rebels around the school and reinforcements were seen heading towards Khan Assal, according to the watchdog, which collects its reports from a network of activists and medics on the ground.
Air strikes were also reported in the southern province of Daraa, the eastern outskirts of Damascus, the northwestern province of Idlib, the northern province of Raqa and the eastern city of Deir Ezzor.
The latest violence came after 154 people were killed nationwide on Monday: 54 civilians, 41 rebels and 59 regime troops, eight of whom were killed in a suicide car bombing against their checkpoint in Damascus, the Observatory said.