The air raid is believed to have killed a militant linked to two deadly attacks in Tunisia last year, reports said.
US F-15 fighter jets targeted an Islamic State training camp in the city of Sabratha, the Pentagon said.
Noureddine Chouchane, a Tunisian citizen linked to the deadly attacks on a Tunis museum and the Sousse beach resort last year, is believed to have been hiding in the city.
"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.
White House could not confirm if Chouchane was killed in the air strike, Reuters reported. The US had said last year it killed an Iraqi Isis militant known as Abu Nabil al-Anbari, who was thought to be the militant outfit's leader in Libya.
The mayor of Sabratha told the news agency the target of the attack was a building in Qasr Talil district, in which many foreigners were staying.
The municipal authorities said in a statement the building had been rented out to foreigners including Tunisians with suspected links to Isis.
Islamic State has flourished in the North African country with vital proximity to Europe following the 2011 overthrow of despot Muammar Gaddafi.
Gaddafi's home city of Sirte is now Isis' strongest outpost outside of Syria.
Two rival governments are vying for the control of the country, which has descended into chaos. The United Nations is in the process of brokering a unity government in Libya.