Firefighters told WPIX that flames broke out just after 1 a.m. at the Evergreen Court Home for Adults, located at 65 Lafayette St. in Spring Valley.
The large facility contains around 200 beds.
Video from overnight showed a portion of the structure collapsing amid the raging inferno.
At one point, multiple people were trapped inside the facility as the fire grew, according to crews on the scene.
Firefighters said they helped evacuate “a number of residents” from facility and brought them to safe locations.
Video showed at least one person being taken from the scene on a stretcher, but it was not immediately clear if there were any serious injuries, or how many civilians may have been injured.
The Greater New York Red Cross said the city asked them to be on standby and that all the residents evacuated had been moved to neighboring facilities.
Firefighters from across the region responded to help ensure resident safety and try to control the blaze.
One firefighter became trapped inside the burning building for some time but was able to escape. That firefighter was being treated for injuries, emergency responders said.
As of 5:30 a.m., flames, and dark, billowing smoke could still be seen coming from both ends of the facility.
Orange & Rockland Utilities said they cut power to the immediate area around the scene of the fire.