There was no immediate word on whether the operation was successful.
Rear Adm. John Kirby, Defense Department press secretary, disclosed the action in a brief statement Monday evening.
"U.S. military forces conducted an operation in Somalia today against the al-Shabab network. We are assessing the results of the operation and will provide additional information as and when appropriate,'' he said.
No other details were released.
NBC news, citing an unnamed U.S. official, reported that a drone fired Hellfire missiles at two vehicles in southern Somalia and that the primary target was al-Shabab's top leader, Ahmed Abdi Godane.
The action comes after Somalia's government forces regained control of a high-security prison in the capital, Mogadishu, that was attacked Sunday by heavily armed suspected jihadists who attempted to free other extremists held there.
Kirby did not say whether the U.S. action was related to the prison attack.
The Godka Jilacow prison is an interrogation center for Somalia's intelligence agency, and suspected militants are believed to be held there.
Also on Monday, the African Union Mission in Somalia (AMISOM) announced its forces, working jointly with the Somalia National Army, liberated several towns as they advance on their main target: the strategic town of Jalalaqsi.
"The Somali National Army supported by AMISOM forces have faced little resistance from their advancement as al-Shabab simply melted away when they heard the aligned forces are approaching," AMISOM announced in a statement.
The Washington Post reported that journalists in Somalia said suspected U.S. drones fired missiles near the port city of Barawe, a stronghold for al-Shabab.
It was al-Shabab gunmen who attacked the upscale Westgate Mall in Nairobi, Kenya, last year, killing at least 67 people.