It happened at around 10.30 p.m. on Tuesday night at the Broadway Liquor Store on Shaw and Marty.
Officers say the suspect is an African-American man and was dressed in black clothing.
He walked into the store, pulled out a gun and ordered the clerk to give him the money.
"He brandished a handgun, pointed it at the victim, and demanded cash from the register and the safe," said Fresno Police Lt. Jerardo Chamalbide.
The suspect took off on foot northbound on Marty.
Police do have surveillance video from the store and are looking for clues to the suspect's identity.
No one was hurt.
Anyone with information is asked to call Fresno Police.