The man walked into the shop at around 11.15am, threatened staff and made off with a quantity of cash, said Sussex Police. No one was hurt, the force confirmed.
Police said the assailant made no attempt to disguise himself. He is described as white, mid-50s, 5ft 8in tall of slim build with short brown hair.
Detective Inspector Catherine O’Connor said: "This brazen man walked into the travel agent on a very busy street in the centre of Brighton, did you see anything?
“Although he hadn’t covered his face, did you see a man leaving the area in a hurry at 11.20am?"