The soldiers were killed about 9:15 p.m. Thursday when their base near Basra's airport was hit by "indirect fire," the military said, referring to an attack by mortars or rockets.
U.S. troops recently took over for departing British forces and are housed outside of Iraq's second-largest city.
The identity of the soldiers killed have not yet been released. An investigation into their deaths is under way.
Violence has dropped off sharply - especially in southern Iraq - since last year, when U.S. and Iraqi forces routed Shiite militias from their strongholds in Basra. Iraqi officials, however, have expressed concern that some of the extremists are seeking to re-ignite the violence.