Three men - one with a handgun and the other two with hammers - threatened staff at the Watches of Switzerland store on Oxford Street on Thursday evening, police said last night.
The looters destroyed a glass cabinet and grabbed a number watches worth an estimated half a million pounds before running away.
No shots were fired and nobody was injured, with officers now appealing for the public's help in tracing the whereabouts of the assailants.
No arrests have been made so far, the BBC reported.
Student Lara Dos Santos tweeted: "I'm actually shaking from seeing this! Armed robbery in Swiss watch store at this time in Oxford street.
"I actually couldn't believe my eyes when I saw the three armed guys all in black ... Scene from a movie," she wrote minutes after witnessing the attack.
In June last year, four men had attacked London's Selfridges store and looted jewellery including watches worth about 1.5 million pounds.
In October, four men were charged in connection the smash-and-grab raid.
