Smoke poured out of the two-story building on 72-10 Myrtle Avenue in Glendale just before 9.
The multi-purpose building contains a Farmer's Market grocery store on the first floor as well as an equipment store.
Nearly 200 firefighters responded to the scene.
Two firefighters suffered serious injuries.
The FDNY brought the fire under control at about 1 a.m. and continued putting out hot spots for several more hours.
The building appeared to be a total loss.
The cause of the blaze is under investigation.