The overnight assault marked the expansion of the U.S.-led air campaign from Iraq to neighboring Syria, signaling a significant escalation in the conflict.
The aerial bombardment struck across several areas of northern Syria, from close to Aleppo in the northwest near Turkey to the Iraqi border, more than 220 miles to the east, according to a statement from the U.S. Central Command and activist accounts on the ground.
The principal target was the Islamic State militant group, formerly known as the Islamic State of Iraq and Syria, or ISIS, which has seized territory across Syria and Iraq and has been labeled by Washington as a threat to regional security.
The attacks, U.S. authorities said, were aimed at Islamic State targets in the vicinity of four Syrian cities -- Raqqa, in north-central Syria, considered the nerve center and operational base of the Islamic State; Dair Elzur, southeast of Raqqa along the Euphrates River; Hasakah, a provincial capital in northeast Syria; and Abu Kamal, along the Iraqi border. All four towns are known Islamic State strongholds.
Participating in the strikes were fighter jets, bombers, armed drones and Tomahawk missiles launched from U.S. vessels in the Persian Gulf and Red Sea, the Central Command statement said. Taking part in the operation, the U.S. said, were five Arab nations -- Bahrain, Jordan, Saudi Arabia, Qatar and the United Arab Emirates.
The Arab countries' contribution was not specified, though the Jordanian government said its air force had destroyed "terrorist" targets.
All the planes involved returned safely to their bases, U.S. officials said.
The strikes "destroyed or damaged" multiple Islamic State targets, the Pentagon said, including "fighters, training compounds, headquarters and command and control facilities, storage facilities, a finance center, supply trucks and armed vehicles."
There was no direct confirmation of airstrikes near the northern Syrian border town of Ayn al-Arab, known as Kobane in Kurdish, which is held by Kurdish militiamen who are arch-enemies of the Islamist forces. Islamic State militants are launching a frontal assault on the Kurdish-held town, prompting more than 100,000 mostly Kurdish refugees to flee across the border to Turkey in recent days.
Separately, the United States conducted eight airstrikes west of Aleppo targeting a militant faction known as the "Khorasan Group," a shadowy network of "seasoned Al Qaeda veterans" that was allegedly plotting an "imminent attack ... against the United States and western interests," the Central Command statement said, without elaboration.
Activists on the ground reported that the attacks near Aleppo targeted the Nusra Front, the official Al Qaeda franchise in Syria, which has often fought alongside U.S.-backed rebels. Aerial strikes hit Nusra centers in Aleppo and nearby Idlib provinces, according to the Syrian Observatory for Human Rights, a Syrian opposition-aligned monitor based in Britain. The group reported seven fighters and eight civilians killed in the strikes.
The airstrikes on Raqqa and its suburbs began around 3 a.m. local time and included more than 18 attacks, said Abu Khalil, a nickname for an activist in the city who posted some of the earliest photos of the aftermath online. He uses a pseudonym for security reasons.
Seven airstrikes struck inside the city, with most targeting the provincial government offices that serve as the major headquarters for Islamic State militants, the activist said. The airstrikes also struck the Islamic State's security branch building, a military training camp, a checkpoint and a pair of former government military bases recently seized by the Islamic State, according to the activist.
There were no accurate numbers for casualties from the strikes. Most residents were either sheltered in their homes during the pre-dawn attacks or sought safety in basements, the activist said.
After the airstrikes, the militants fled their headquarters, said Abu Khalil.
"Of course the people are scared," Abu Khali said, adding that public opinion was divided about the U.S. airstrikes. "If the targeting is precise on ISIS, then I am for it."
In recent weeks, activists and others say, the Islamic State has been moving much of its leadership and heavy weapons out of Raqqa, anticipating a U.S. aerial assault. President Obama announced on Sept. 10 that U.S. forces may target the Islamic State inside Syria as part of a U.S. effort to "degrade and ultimately destroy" the Islamic State.
Staff writer Abdulrahim contributed from Irbil, Iraq. Special correspondent Nabih Bulos in Beirut also contributed.