More than 75 firefighters tackled the blaze at Selsey Academy in School Lane in West Sussex as huge plumes of black smoke were seen emanating from the site.
The cause of the fire has not yet been established and no injuries have been reported so far.
"People in vicinity of smoke from Selsey school fire advised to stay clearof smoke, stay indoors and keep windows closed," West Sussex Fire and Rescue Service said.
Chairman of governors for the school, Bill Emerson, told BBC: "There is a possibility we might be able to save a small section of the school and the emergency services are doing their best to do that. But it is amazing how quickly the fire has spread.
The Academy is a mixed school for pupils aged 11 to 16.
Hampshire Fire and Rescue Service has sent crews to help West Sussex colleagues and South East Coast Ambulance Service is also at the scene.
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