The shooting occurred around 1:25 a.m. (0525 GMT) in the southern Georgia city of Vienna, the State Bureau of Investigation said in a statement, Xinhua reported.
Two men aged 21 and 23 were pronounced dead at the scene, said County Sheriff Craig Peavy, adding that the injured were taken to regional hospitals.
More than 1,000 people had gathered for the block party when at least 50 shots were fired, Peavy said, noting that most of the injured were wounded by gunfire, while others were struck by cars as people fled the scene.
Authorities have not yet identified any suspects or named a potential motive for the shooting.