The men entered the shop for luxury timepieces at 11 Grendelstrasse shortly after 2pm and threatened two saleswomen with a gun, Lucerne cantonal police said.
After that they removed watch display cases and sprayed the employees with pepper before fleeing on foot, police said.
Investigators have released several images of the suspects taken by surveillance cameras, showing men with short hair and not wearing face masks.
One man is seen wearing a striped jacket, scarf and jeans, while the others seem to be lightly dressed, with two of them appearing to be without jackets.
A fourth man is seen wearing a hooded top with broad black and yellow horizontal stripes.
The Lucerne cantonal prosecutor’s office is involved in the investigation.
The Blick newspaper reported that the four men changed their clothes on the run.
The robbed boutique is owned by the Bucherer group, whose headquarters are in a nearby Lucerne square.
Bucherer spokesman Jörg Baumann confirmed the robbery to Blick but would not comment on the extent of the loss.