Officers responded to the Valero on Shields and Clovis Avenue just before 5 am, where they found the 37-year-old victim suffering from multiple gunshot wounds.
Paramedics were called to the gas station and transported the man to the hospital, where he later died. His name has not been released.
Investigators say they believe the man was followed inside the store before the gunfire erupted.
A motive for the attack has not been determined, but police say this was not a robbery.
Detectives said a suspect was seen leaving the area in a dark-colored vehicle. No further information was immediately available.
The gas station will remain blocked off as homicide detectives continue their investigation. Traffic in the area has not been impacted.
Anyone with information is asked to call the Fresno Police Department.