BEIRUT, Lebanon — Insurgents breached Syria’s largest city Friday and clashed with government forces for the first time since 2016, according to a war monitor and fighters, in a surprise attack that sent residents fleeing and added fresh uncertainty to a region reeling from multiple wars.

The advance on Aleppo followed a shock offensive launched by insurgents Wednesday, as thousands of fighters swept through villages and towns in Syria’s northwestern countryside. Residents fled neighborhoods on the city’s edge because of missiles and gunfire, according to witnesses in Aleppo. The Syrian Observatory for Human Rights, which monitors the country’s unresolved civil war, said dozens of fighters from both sides were killed.

The attack injected new violence into a region experiencing dual wars in Gaza and Lebanon involving Israel, and other conflicts, including the Syrian civil war that began in 2011.

Aleppo has not been attacked by opposition forces since they were ousted from eastern neighborhoods in 2016 following a grueling military campaign in which Syrian government forces were backed by Russia, Iran and its allied groups.

But this time, there was no sign of a significant pushback from government forces or their allies. Instead, reports emerged of government forces melting away in the face of advances, and insurgents posted messages on social media calling on troops to surrender.

Robert Ford, who was the last U.S. ambassador to Syria, said the attack showed that Syrian government forces are “extremely weak.” In some cases, he said, they appear to have “almost been routed.”

This week’s advances were among the largest in recent years by opposition factions, led by the Hayat Tahrir al-Sham group, or HTS, and represent the most intense fighting in northwestern Syria since 2020, when government forces seized areas previously controlled by the opposition.

The offensive came as Iran-linked groups, primarily Lebanon’s Hezbollah, which has backed Syrian government forces since 2015, have been preoccupied with their own battles at home.

A ceasefire in Hezbollah’s two-month war with Israel took effect Wednesday, the day the Syrian opposition factions announced their offensive. Israel has also escalated its attacks against Hezbollah and Iran-linked targets in Syria during the last 70 days.

Dareen Khalifa, a senior adviser with the International Crisis Group and an expert on Syrian groups, said the insurgents have signaled for a while that they were ready for an offensive. But no one expected the swift advance of the forces toward Aleppo.

“It’s not only that the Russians are distracted and bogged down in Ukraine, but also the Iranians are distracted and bogged down elsewhere. Hezbollah’s distracted and bogged down elsewhere, and the regime is absolutely cornered,” she said. “But the surprise element comes in with how quickly the regime crumbled.”

The attack on Aleppo followed weeks of simmering low-level violence, including government attacks on opposition-held areas. Turkey, which has backed Syrian opposition groups, failed in its diplomatic efforts to prevent the government attacks, which were seen as a violation of a 2019 agreement sponsored by Russia, Turkey and Iran to freeze the line of the conflict.

Turkish security officials said Thursday that Syrian opposition groups initially launched a long-planned “limited” offensive toward Aleppo, where attacks targeting civilians originated. However, the offensive expanded as Syrian government forces began retreating from their positions, the officials said.

The aim of the offensive was to reestablish the boundaries of the de-escalation zone, according to Turkish officials.

The 2016 battle for Aleppo was a turning point in the war between Syrian government forces and rebel fighters after 2011 protests against Bashar Assad’s rule turned into an all-out war.

Russia and Iran and its allied groups helped Syrian government forces reclaim control of the city that year after a grueling military campaign and a siege that lasted for weeks.

Besides backing opposition forces, Turkey has also established a military presence in Syria, sending troops into parts of the northwest. Separately and largely in the east of Syria, the United States has supported Syrian Kurdish forces fighting Islamic State militants.

The Syrian government did not comment on insurgents breaching Aleppo city limits.

The Kremlin said Friday that it considered the attack an encroachment on Syria’s sovereignty and that it supported the quickest possible establishment of constitutional order in the region.

“Of course, this is a violation of Syria’s sovereignty in this region,” Russian presidential spokesperson Dmitry Peskov told a press briefing.

Syria’s armed forces said in a statement Friday that they clashed with insurgents in the countryside around Aleppo and Idlib, destroying drones and heavy weaponry. They vowed to repel the attack and accused the insurgents of spreading false information about their advances.

The Syrian Observatory for Human Rights said the insurgents detonated two car bombs Friday at the western edge of Aleppo. The war monitor said insurgents were also able to seize control of Saraqeb, south of Aleppo, a town at the strategic intersection of the highways linking Aleppo with Damascus and the coast. Syrian government authorities diverted traffic from that highway Thursday.

An insurgent commander posted a recorded message on social media calling on Aleppo residents to cooperate with the advancing forces.

Turkey’s state-run Anadolu Agency reported that the insurgents entered the city center Friday and now control about 70 locations in Aleppo and Idlib provinces.

Syria’s state media reported that projectiles from insurgents landed in student accommodations at Aleppo’s university in the city center, killing four people, including two students.

Syrian armed forces said the insurgents are violating a 2019 agreement that de-escalated fighting in the area, the last remaining opposition stronghold for years.

Hezbollah was “the main force” in the government’s control of Aleppo, said Rami Abdurrahman, head of the Observatory.

In a phone call with his Syrian counterpart, Iranian Foreign Minister Abbas Araghchi described the insurgent attacks in Syria “as a plot orchestrated by the U.S. and the Zionist regime following the regime’s defeat in Lebanon and Palestine.”

Insurgents posted videos online showing they were using drones, a new weapon for them. It was not clear to what extent the drones were used on the battleground.

Insurgents attacked a military airbase southeast of Aleppo with drones early Friday, destroying a helicopter, the Anadolu Agency reported. The opposition groups also seized heavy weapons and military vehicles belonging to the government forces, the agency said.

Associated Press writers Suzan Fraser in Ankara, Turkey; Albert Aji in Damascus, Syria; and Ellen Knickmeyer in Washington contributed to this report.