The robbery happened at Ladbrokes in Rowlands Road at around 5.50pm yesterday (April 24), police said.
A man entered the betting shop and threatened staff with a knife and stole a sum of money before fleeing the premises towards Shelley Road, a police spokesman said.
Officers, assisted by the police helicopter, attended the scene and conducted an area search but the suspect was not found.
A Sussex Police spokesman said: “The suspect is described as white, of slim build and wearing white trousers, a trench coat and a scarf around his face.
“If anyone has information to aid the investigation please report online or call 101 quoting reference 1032 of 24/04.”