Firefighters arrived to flames shooting out of every window of the Elm Street home just before 4:45 a.m. Friday.
The wind-driven flames jumped to another house on North Terrace Avenue but were quickly extinguished.
All five residents of the Elm Street multi-family home were able to evacuate.
"We got everyone out of the houses and while they were fighting that house, this one caught, and that one caught, and it was a mess out here," said Felicia Franklin, a neighbor.
Four were treated for smoke inhalation. Two of them went to Jacobi Hospital, and the youngest was a 3-year-old.
Firefighters battled the wind and rough overnight conditions.
"It was the wind, it was the weather, it is very challenging. We had ice, we had to get people to put salt on the ice. We had a lot of slips and falls. It was very difficult to put this fire out," said Deputy Chief Juan Peralta, Mount Vernon Fire Department.
One firefighter slipped on the ice created by freezing water, but he was treated for a minor injury and continued to battle the blaze.
Two houses on North Terrace Avenue suffered water damage, but the structure on Elm Street with four apartments is completely gutted.
"It's heartbreaking, it's heartbreaking, but I'm happy that no one got seriously hurt, that's the important thing," said John Joy, landlord. "I mean, the house can be replaced you know, families can't be replaced."
The Red Cross is helping to relocate 14 residents who have been displaced.
It was the second major fire in Mount Vernon of the night. Hours earlier, 25 people were left homeless by a fire at 85 Gramatan Ave. Three people were taken to Jacobi Hospital for smoke inhalation.
Firefighters were just finishing fighting that fire when they responded to the one on Elm Street.
The cause of the fire is under investigation.
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