The two five-story buildings on a corner of 116th Street and Park Avenue in East Harlem collapsed at about 9:30 a.m., sending smoke wafting into Central Park and blowing out windows because of the concussion, WNBC-TV, New York, reported.
Witnesses said they felt the earth rumble as far away as 150th Street. Closer to the site, groceries fell from store shelves and debris floated through the air.
New York Mayor Bill de Blasio said the residential buildings were destroyed and first responders were combing through the rubble. Trained dogs assisted in the search.
"This is a tragedy of the worst kind because there was no indication in time to save people," de Blasio said.
At least two women and a man were confirmed dead, the New York Times said. A senior city official said city personnel had received reports of more than a dozen people who couldn't be reached but cautioned that the missing may simply be unavailable by phone.
The only indication that anything was wrong before the blast was a call to Con Edison from a nearby building to report a strong odor of gas just minutes before the explosion, the mayor and the utility said.
The Fire Department said hundreds of firefighters and other first responders were working the scene to fight smoldering fires and search for victims.
Officials said the process would take time.
"We have to be very careful," Fire Commissioner Salvatore Cassano said. "The building is in a very precarious position."
Firefighters also said they were working to seal windows in nearby buildings that were blown out in the blast.
The city's Buildings Department said one of the collapsed buildings had six rental units and the other had nine, WNBC said.
The explosion blew debris onto the elevated tracks of the Metro-North commuter line tracks above Park Avenue, forcing a service shutdown in both directions.
About 250 firefighters from 44 units responded, the Times said. During the late afternoon, they were seen sifting through the wreckage and passing buckets of debris from one to another to clear the site.
The National Transportation Safety Board said it sent a team, led by Pipeline Investigator Ravi Chhatre, from Washington to investigate the explosion.