The US military said an unmanned aircraft fired a Hellfire missile and killed six "heavily armed criminals" at around 9:45pm local time (1845 GMT) on Thursday.
It said the missile was fired after the drone observed a large group of people with rocket-propelled grenade launchers and mortar tubes.
Two previous air strikes announced by the military on Thursday killed six people in similar cricumstances.
'Mortar team' hit
The strike in Basra happened when US aircraft homed in on the northern al-Hayaniya district after identifying a group of fighters, Major Tom Holloway, the British spokesman, said.
"The air strike was launched after positively identifying a mortar team that was engaging the Iraqi troops on the ground."
Basra was rocked by fierce clashes last month after Nuri al-Maliki, the Iraqi prime minister, ordered a crackdown on Shi armed groups, mostly from the Mahdi Army of Muqtada al-Sadr, the Shia leader.
Sporadic fighting is still reported from Basra, especially in Hayaniya.
Ongoing clashes
Battles have raged since Sunday between Iraqi and US forces and Shia fighters from the Mahdi Army in the militia's eastern Baghdad bastion of Sadr City.
Iraqi officials claim around 80 people have been killed, with scores wounded.
Al-Sadr's movement said on Thursday it was "under siege" in the district and warned that its militia was ready to take up arms again, breaking a ceasefire ordered by him last August.