Officers responded to a Shotspotter call just before 5 am on Holland Avenue and Fresno Street, north of Ashlan Avenue.
Police say a man in his 20s was taken to Community Regional Medical Center, where he later died.
Investigators say more than 20 rounds were fired.
Detectives are now canvassing the area and looking for possible witnesses.
Authorities have blocked off Holland Avenue between Fresno Street and Augusta Street. Drivers are advised to avoid the area.
Anyone with information is asked to call the Fresno Police Department.