The thunderous explosion at the John F Kennedy High School in the Bronx neighbourhood ripped through the fourth, fifth and sixth floors of the building, blowing out windows and causing extensive damage, New York City Mayor Bill de Blasio said.
The blast occurred at around 8 pm last night during a construction work, injuring three contractors - one critically - who were working to fix up a science lab on the sixth floor.
The Mayor reached the scene of the explosion to assess the damage.
He said that details still emerging about the explosion and a full investigation is underway to find out the cause of the blast.
He said energy company ConEdison "confirmed" that the explosion was "gas-related".
The schools in the city are currently closed and will open for the the new session in September.
At least three floors of the building were heavily damaged, officials told CBS2. Photos at the scene showed windows blown out and debris scattered in the vicinity of the building.
Emergency workers, police and crews from the energy company have rushed to the scene to bring rescue efforts.
The school enrolls a total of 1,291 students, according to the Department of Education.
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