It started around 5:30 a.m. Sunday at a vacant building on Topping Avenue near 174th Street in the Claremont section and spread to a neighboring home.
The fire was declared under control just after 8 a.m.
More than 130 firefighters responded to the scene. There were two minor injuries, one suffered by a firefighter, the other a civilian.
Four families who lived in the home were displaced, and are being assisted by the Red Cross.
There is no word yet on the cause of the fire, but investigators say it started in the building's basement.