The gunman targeted crowds near the Perkins Square Baptist Church in Baltimore, Maryland.
Cops rushed to the scene at around 5.30pm Sunday local time (10.30pm BST).
Police confirmed one victim have died — but they have not been named.
The conditions of the other victims aren’t known.
Residents told US media a car pulled up and began firing while a neighbourhood cookout was taking place near the church.
“Someone knows something”
Bernard Young, Acting Mayor, Baltimore
The gunman is believed to still be on the loose after fleeing the scene in a car.
Authorities have asked for the public’s help to identify the gunman after the attack near the 2500 block of Edmondson Avenue in the west of the city.
Baltimore Police Commissioner Michael Harrison said it appears the gunman was targeting someone in the crowd.
“We know that many people were out here,” he said.
“It is only with the community’s help that we will be able to identify those responsible.”
The city’s acting Mayor Bernard Young also begged the public for information.
“Someone knows something,” he insisted.
It comes as authorities in the US are on high alert following devastating attacks on places of worship in the country.
On Saturday, one woman was killed and three others injured after a shooting at a California synagogue.
John Earnest, 19, is believed to have stormed the Chabad of Poway, near San Diego, while worshippers gathered for the final day of Passover.
Cops said the gunman — wearing a helmet and a bulletproof vest — began shooting at the synagogue.
He was only stopped when a hero off-duty Border Patrol officer began firing back.