It was the second U.S. air strike in three months against Islamic State in Libya, where the hardline Islamist militants have exploited years of chaos following Muammar Gaddafi's 2011 overthrow to build up a presence on the southern shores of the Mediterranean Sea. The Pentagon said it had targeted an Islamic State training camp and killed a Tunisian militant linked to major attacks on tourists in Tunisia.
The mayor of the Libyan city of Sabratha, Hussein al-Thwadi, told Reuters the planes struck at 3:30 am (0130 GMT), hitting a building in the city's Qasr Talil district, home to many foreigners.
He said 41 people had been killed and six wounded. The death toll could not immediately be confirmed with other officials.
Photos released by the municipal authorities showed a massive crater in grey earth. Several wounded men lay bandaged in hospital.
The air strikes targeted a house in a residential district about 8 km (5 miles) west of the centre, the municipal authorities said in a statement.
The house had been rented to foreigners including Tunisians suspected of belonging to Islamic State, and medium-calibre weapons including machineguns and rocket-propelled grenades had been found in the rubble, the statement said.
Tunisian security sources have said they believe Tunisian Islamic State fighters have been trained in camps near Sabratha, which is close to the Tunisian border.
Among those Washington said it targeted in the air strikes was Noureddine Chouchane, a Tunisian blamed by his native country for attacks last year on a Tunis museum and the Sousse beach resort, which killed dozens of tourists.
"Destruction of the camp and Chouchane's removal will eliminate an experienced facilitator and is expected to have an immediate impact on ISIL's ability to facilitate its activities in Libya, including recruiting new ISIL members, establishing bases in Libya, and potentially planning external attacks on U.S. interests in the region," the Pentagon said, using an acronym for Islamic State, also known as ISIS or Daesh.
The air strikes came just days after a warning by President Barack Obama that Washington intended to "take actions where we've got a clear operation and a clear target in mind".
"And we are working with our coalition partners to make sure that as we see opportunities to prevent ISIS from digging in, in Libya, we take them," Obama said on Tuesday.
Britain said it had authorised the use of its airbases to launch the attack.
"I welcome this strike that has taken out a Daesh training camp being used to train terrorists to carry out attacks," Defence Secretary Michael Fallon said in a statement.
"I was satisfied that its destruction makes us all safer, and I personally authorised the U.S. use of our bases."
Islamic State runs a self-styled caliphate across swathes of Iraq and Syria, where it has faced air strikes from a U.S.-led coalition since 2014.
Thwadi, the Sabratha mayor, said some Tunisians, a Jordanian and two women were among the dead, and several Tunisians who had recently arrived in Sabratha were among survivors. He gave no further details.
Since Gaddafi was overthrown five years ago by rebel forces backed by a campaign of Nato air strikes, Libya has slipped deeper into chaos, with two rival governments each backed by competing factions of former rebel brigades.
A U.N.-backed government of national accord is trying to win support, but is still awaiting parliamentary approval. It is opposed by factional hardliners and has yet to establish itself in the capital Tripoli.
Meanwhile, Islamic State has expanded, attacking oil ports and taking over Gaddafi's home city of Sirte, now the militant group's most important stronghold outside its main redoubts in Syria and Iraq.
Calls have increased for a swift Western response to stop the group establishing itself more permanently and using Libya as a base for attacks on neighbours Tunisia and Egypt.