A statement by the U.S. Africa Command said the strike was carried out Friday night in Lower Shabelle region, about 20 miles (32 kilometers) north of the capital, Mogadishu. It came a day after another strike in the Bay Region, about 100 miles west of Mogadishu.
Friday's airstrike was the 23rd the U.S. military has carried out this year against the al-Qaida-linked al-Shabab and the far smaller Islamic State group in Somalia. The Trump administration earlier this year approved expanded military operations against extremists in the Horn of Africa nation.
The latest U.S. drone strike was carried out in coordination with Somalia's government, the U.S. statement said.
Separately, Somalia's Information Minister Abdirahman Osman on Saturday said 81 al-Shabab fighters were killed in an operation by Somali security forces in Jilib district, with the extremists' camp there destroyed.
Al-Shabab, the deadliest Islamic extremist group in Africa, has been blamed for the massive truck bombing in Mogadishu last month that killed more than 350 people. It was Somalia's worst-ever attack and one of the world's deadliest in years.
Earlier this month, the U.S. carried out its first airstrike against ISIS fighters in Somalia, targeting a small but growing cell that emerged in the northern Puntland region just two years ago. Many of the fighters split off from al-Shabab.
While Somalia's president has vowed a "state of war" in response to last month's attack, concern is growing about the gradual security handover that has begun from a 22,000-strong African Union force to Somali national forces.
The AU this week announced the beginning of its withdrawal from the long-chaotic and still heavily fractured nation, saying it will cut 1,000 troops by the end of the year. The AU pullout is set to be complete by the end of 2020.
Copyright 2018 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.