Pentagon spokeswoman Maj. Audricia M. Harris said the strike occurred Sunday afternoon Somalia time and the US was assessing the results.
She did not call it a drone strike. Somali officials have said the US has carried out several drone strikes in recent years against the al-Qaida-linked al-Shabab.
The airstrike follows one in June that the US said killed eight Islamic extremists at a rebel command and logistics camp in the country's south.
President Donald Trump has approved expanded military operations against al-Shabab, including more aggressive airstrikes and considering parts of southern Somalia areas of active hostilities.
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The US in April announced it was sending dozens of regular troops to Somalia in the largest such deployment there in roughly two decades, saying it was for logistics training of Somalia's army.
The Horn of Africa nation is trying to rebuild after more than two decades as a failed state, and its chaos helped in the rise of al-Shabab. Now a new threat has emerged in the country's north with fighters claiming alliance to the Islamic State group.
Pressure is growing on Somalia's military to assume full responsibility for the country's security. The 22,000-strong African Union multinational force, AMISOM, which has been supporting the fragile central government, plans to start withdrawing in 2018 and leave by the end of 2020.
The US military has been among those expressing concern that Somalia's forces are not yet ready.