Local residents told the BBC that an al-Shabab commander and four others were killed but US officials say this has not been confirmed.
The strike was aimed at a vehicle in a remote area of southern Somalia, near the coastal town of Barawe.
Al-Shabab is the main al-Qaeda-linked group in East Africa.
The Pentagon says the target was a senior leader in the two organisations.
Local residents told BBC Somalia correspondent Mohamed Mwalimu that al-Shabab commander Sahal Iskudhuq and the others had been killed as they were travelling in a convoy which was hit by a missile.
Al-Shabab fighters cordoned off the area after the attack, they added.
The group has not yet commented.
Iskudhuq was said to be close to al-Shabab leader Ahmed Godane, with a large number of fighters under his control, our correspondent says.