A fighter for the moderate Free Syrian Army sits in a shooting position behind sandbags during clashes with loyalist forces in Aleppo, Syria, on Nov. 2. Moderate rebels elsewhere in northern Syria were pushed back by Islamists over the weekend. (Hosam Katan/Reuters)

The Obama administration’s Syria strategy suffered a major setback Sunday after fighters linked to al-Qaeda routed U.S.-backed rebels from their main northern strongholds, capturing significant quantities of weaponry, triggering widespread defections and ending hopes that Washington will readily find Syrian partners in its war against the Islamic State.

Moderate rebels who had been armed and trained by the United States either surrendered or defected to the extremists as the Jabhat al-Nusra group, affiliated with al-Qaeda, swept through the towns and villages the moderates controlled in the northern province of Idlib, in what appeared to be a concerted push to vanquish the moderate Free Syrian Army, according to rebel commanders, activists and analysts.

Other moderate fighters were on the run, headed for the Turkish border as the extremists closed in, heralding a significant defeat for the rebel forces Washington had been counting on as a bulwark against the Islamic State.

Moderates still retain a strong presence in southern Syria, but the Islamic State has not been a major factor there.

A senior Defense Department official said the Pentagon “is monitoring developments as closely as possible” but could “not independently verify” reports from the ground. The official was not authorized to comment publicly and spoke on the condition of anonymity.

Moderate rebels run with their weapons during clashes with loyalist forces in Aleppo. Defeats to moderate rebels elsewhere in northern Syria will isolate rebels in Aleppo, who are fighting to hold at bay both the Islamic State and loyalists. (Hosam Katan/Reuters)

Jabhat al-Nusra has long been regarded by Syrians as less radical than the breakaway Islamic State faction, and it had participated alongside moderate rebels in battles against the Islamic State earlier this year. But it is also on the U.S. list of terrorist organizations and is the only group in Syria that has formally declared its allegiance to the mainstream al-Qaeda leadership.

A Jabhat al-Nusra base was one of the first targets hit when the United States launched its air war in Syria in September, and activists said the tensions fueled by that attack had contributed to the success of the group’s push against the moderate rebels.

“When American airstrikes targeted al-Nusra, people felt solidarity with them because Nusra are fighting the regime, and the strikes are helping the regime,” said Raed al-Fares, an activist leader in Kafr Nabel, in Idlib.

“Now people think that whoever in the Free Syrian Army gets support from the U.S.A. is an agent of the regime,” he said.

Fleeing rebel fighters said they feared the defeat would spell the end of the Free Syrian Army, the umbrella name used by the moderate rebel groups that the United States has somewhat erratically sought to promote as an alternative both to the Assad regime and the extremist Islamic State.

Among the groups whose bases were overrun in the assault was Harakat Hazm, the biggest recipient of U.S. assistance offered under a small-scale, covert CIA program launched this year, including the first deliveries of U.S.-made TOW antitank missiles. The group’s headquarters outside the village of Khan Subbul was seized by Jabhat al-Nusra overnight Saturday, after rebel fighters there surrendered their weapons and fled without a fight, according to residents in the area.

Hussam Omar, a spokesman for Harakat Hazm, refused to confirm whether American weaponry had been captured by the al-Qaeda affiliate because, he said, negotiations with Jabhat al-Nusra are underway.

Harakat Hazm, whose name means “Steadfastness Movement,” had also received small arms and ammunition alongside non-lethal aid in the form of vehicles, food and uniforms from the United States and its European and Persian Gulf Arab allies grouped as the Friends of Syria alliance. Scores of its fighters had received U.S. training in Qatar under the covert program, but it was also not possible to confirm whether any of those fighters had defected to the al-Qaeda affiliate.

Another Western-backed group, the Syrian Revolutionary Front, on Saturday gave up its bases in Jabal al-Zawiya, a collection of mountain villages that had been under the control of the pro-American warlord Jamal Maarouf since 2012. A video posted on YouTube showed Jabhat al-Nusra fighters unearthing stockpiles of weaponry at Maarouf’s headquarters in his home town of Deir Sunbul.

In a separate video, Maarouf, addressing the Jabhat al-Nusra leadership, said he fled along with those of his men who had not defected, “to preserve the blood of civilians, because you behead people and slaughter them if they do not obey you.”

The loss of northern Idlib province could prove a crippling blow to the moderate rebels, whose fight against Assad’s regime began in 2012 and has since been complicated by the rise of rival Islamist groups with goals very different from those of the original revolutionaries.

Idlib was the last of the northern Syrian provinces where the Free Syrian Army maintained a significant presence, and groups there had banded together in January to eject the Islamic State in the first instance in which Syrians had turned against the extremist radicals.

Most of the rest of northern Syria is controlled by the Islamic State, apart from a small strip of territory around the city of Aleppo. There the rebels are fighting to hold at bay both the Islamic State and the forces of the Assad government, and the defeat in Idlib will further isolate those fighters.

Perhaps most significant, it will complicate the task of finding Syrian allies willing to join the fight against the Islamic State, said Charles Lister of the Qatar-based Brookings Doha Center.

“The United States and its allies are depending very strongly on having armed organizations on the ground to call upon to fight the Islamic State, and now those groups have taken a very significant defeat,” he said.

Although some groups have already been receiving U.S. support, it was never sufficient to tilt the balance of power on the ground, Lister said. “This sends a message that Western support doesn’t equal success,” he added.

The limited assistance program already underway is expected to be supplemented by a bigger, overt, $500 million program to train and equip moderate rebels that was first announced by President Obama in June and that has become a central component of the U.S. strategy to confront the Islamic State.

But U.S. officials have said it could be months before the program starts, and longer before it takes effect, thereby giving an incentive to the moderates’ foes to challenge them before any significant help arrives.

Although the administration has long voiced its support for the rebel fighters, direct U.S. aid to them has been slow and scant, with weapons shipments and a CIA training program limited by the need to vet the fighters for any ties to militants.

More extensive aid to the rebels has also been withheld in the interest of promoting a negotiated political solution that would remove Assad from power while leaving Syrian institutions, including the military, intact.

In public remarks last week, national security adviser Susan E. Rice acknowledged that the U.S.-backed rebels “are fighting a multifront conflict, which is obviously taking a real toll on them.” The expanded military train-and-equip mission, Rice said, “is, in the first instance, going to enable them to fend off ISIL, but it is also designed and originated with the concept of trying to help create conditions on the ground that are conducive to negotiations. And that means helping them in their conflict against Assad as well.”

Meanwhile, the extension of the air war to Syria in September has drawn widespread complaints from moderate rebels that their goal of ousting the Assad regime is being shunted aside in the effort to fight the Islamic State, which is also known as ISIL. Anecdotal evidence that the airstrikes have indirectly aided the Assad government in its efforts to crush the rebellion has further fueled resentment.

Besides southern Syria, where the Islamic State has not established a significant foothold, moderate groups are also still fighting in scattered pockets around Damascus. But the U.S. campaign against the Islamic State is focused on the northern part of the country, where the group has entrenched itself across vast areas of territory for more than a year.

Suzan Haidamous in Beirut and Karen DeYoung in Washington contributed to this report.