Smoke and flames billowed from the Deja Vu Lounge on Hamilton Street around 3 a.m.
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Firefighters said everyone besides the owners of the club had evacuated by the time they arrived, but the owners were not injured.
Three apartments above the club did sustain smoke damage. Residents had to be evacuated and are currently being assisted by the Red Cross.
Officials said one firefighter was hurt when he fell at the scene. He was transported to an area hospital for treatment.
Investigators said the fire started in the basement and extended to the walls and up to the first floor and loft. It took about an hour to be placed under control.
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The nightclub was the site of a shooting where 10 people were wounded last June.
At least one arrest has been made in connection to that attack.