Students will be turned away from Morningside State School on Tuesday, as investigators pick over the remains of the gutted buildings.
Officers say the size of the blaze suggests arson.
Queensland Fire and Emergency Services Chief Superintendent Lance Duncan said a significant portion of the school was lost.
"We've got three buildings that were interconnected and they were reasonably large structures," he told reporters.
"There's a lot of smoke still issuing from those particular structures at the moment, so it wouldn't be safe to have the kids here."
Two three-story buildings at the school were engulfed in flames by the time fire fighters arrived about 3.30am on Tuesday. The flames quickly spread to other buildings.
Exclusion zones were enforced as the fire raged.
It took more than 50 fire fighters to extinguish the blaze, which destroyed six classrooms.
Air quality tests have since allayed any concerns about asbestos in the air.
Queensland Department of Education Regional Director Helen Kenworthy said she hoped the school would reopen on Wednesday.
"The safety of the students and the staff is our priority," she told ABC radio.
"The site isn't safe, we need to keep people safe so we have closed the school today."
The school was opened in 1926.