It was not immediately clear how many people had been shot, but the Charleston Post and Courier said nine people were hit, some fatally, and officials spoke of their shock at their “tragedy.”
The shooting happened at about 9.pm (0100 GMT) at the Emanuel African Methodist Episcopal Church. According to its website, it is the oldest such church in the US south.
“(My family) and I are praying for the victims and families touched by tonight’s senseless tragedy at Emanuel AME Church,” South Carolina Governor Nikki Haley said in a statement.
“While we do not yet know all of the details, we do know that we’ll never understand what motivates anyone to enter one of our places of worship and take the life of another.”
The Charleston police department said the suspect was a clean-shaven white man, aged about 21. As of midnight (0400 GMT), he was still at large.
Local network ABC4 News earlier said police were also investigating a possible bomb threat.
Charleston is known locally as “The Holy City,” due to its large number of churches and historical mix of immigrant ethnic groups that brought a variety of creeds to the southern city on the Atlantic coast.
The city is also known outside the United States for its namesake 1920s dance.
Police called the fatal shooting a “hate crime”.
“I do believe it was a hate crime,” Charleston Police Chief Gregory Mullen told a news conference. – AFP