Scores of others have been injured in the incident, which sent smoke billowing into the city sky.
More than 250 firefighters tackled the blaze at the scene near 116th Street and Park Avenue.
Train services to and from Grand Central Terminal have been restored after a complete halt earlier.
NYC Mayor Bill de Blasio said in a news conference from the scene that the gas leak had been reported to the utility company 15 minutes before the blast on Wednesday morning.
Bill de Blasio said the “major explosion” had destroyed two buildings and heavily damaged other structures.
The mayor’s office confirmed to the Associated Press news agency that nine people were still missing by early Wednesday evening.
The New York fire department elevated the incident to the highest threat level possible.
The department said 22 people had been hurt, but a tally of local hospitals by ABC News found that 64 had been admitted with injuries as a result of the incident.
That figure included seven children, one of whom was in a critical condition.
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.
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