The raider burst into One Stop in Black Bull Lane at around 10.50pm yesterday, a spokesman for the force said, before aiming his weapon at workers.
He escaped on foot and, despite officers scouring the area, has so far evaded capture.
"We searched the area and were unable to find him at that stage," the spokesman said.
The robber was described as around 5ft10in tall, and was wearing a black top with a white Nike logo.
He is now being hunted by officers.
Nobody was hurt, police added, with the man 'making threats before getting the money, grabbing stuff, and making off'.
Det Sgt Katie Clancy, of Preston CID, added: “This must have been a traumatic ordeal for the staff members involved.
"We are appealing for anyone that was either in the store or in the vicinity from around 10.35pm to 11.10pm to make contact with us if they saw or heard anything suspicious."
A woman at the shop declined to comment to the Post this morning.
At around 3.15pm on Tuesday, October 31, a masked man approached a shop assistant with a large knife and a brown shopping bag before demanding money from the till.
Police said he then fled in a dark Mercedes C-Class car. He was described as white, 5ft8in tall, of a medium build, and aged in his late teens or early 20s.
He was also wearing all black and had his face covered.
The gang, armed with knives and a baseball bat, approached the cigarette kiosk in the store, opposite Royal Preston Hospital, and threatened staff before jumping over the counter and stealing cigarettes and cash from the till.
All the men were wearing dark clothing and balaclavas. Two tried to get into a safe being driving off in a dark-coloured car.
Det Insp Roger Ashcroft, of Lancashire Police, said at the time 'robberies of this type are rare', but urged shoppers and businesses to remain vigilant and to report any suspicious activity.
Officers were called out at around 8.45pm on Friday, November 3 after the raider used a short blade to steal Â£160 in cash and three packets of Lambert and Butler cigarettes.
They were hunting a white man, around 6ft, of a slim build and pale complexion. He was believed to be around 18 or 19 years old.
There was no suggestion the robberies are linked however.