More than 20 people were reportedly injured in the incident, which occurred near 116th Street and Park Avenue.
All train services in and out of Grand Central terminal have been halted following the incident near its track
New York City Mayor Bill de Blasio said in a news conference from the scene that the gas leak had been reported to the utility company just 15 minutes before the blast on Wednesday morning.
At least a dozen individuals were still missing in the area as of Wednesday afternoon.
New York fire department has elevated the incident to the highest threat level possible.
The utility company, Con Edison, says a resident in a nearby building reported smelling gas shortly before the explosion.
Streets and pavements around the site were littered with broken glass from shattered windows.
Witnesses reported the powerful blast knocked items off shelves in nearby stores.
Authorities in the area were said to be handing out medical masks to residents due to the thick white smoke at the scene.
The explosion caused the swift and entire collapse of two buildings in the East Harlem neighborhood of New York on Wednesday, causing at least two deaths and over 20 injuries.