LUX Nightclub on Chapel Street in South Yarra was engulfed in flames early on Thursday, with about 50 firefighters and 15 fire trucks called to battle the blaze.
"Within minutes of the first call, the top area of the LUX Nightclub was fully involved in fire and it was starting to come out through the roof space," Fire Rescue Victoria's Mitch Simons said at the scene.
A smoke warning was issued for local residents and it took crews two hours to bring the fire under control.
The first floor bar was burnt out and its roof rendered a mess of twisted metal. (Joel Carrett/AAP PHOTOS)
No one was injured as the club was closed at the time.
The blaze has been deemed suspicious, with an arson chemist to comb for clues.
"Police will investigate whether the incident is linked to any other recent incidents," a Victoria Police spokeswoman said.
The first floor bar has been burnt out and its roof rendered a mess of twisted metal.
The club is above a Westpac bank and boutique store, which also suffered damage.
Part of Chapel Street will be closed until mid-morning due to the structural damage, disrupting traffic along the major road.
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