A large fire broke out at the former Elmete Wood School in Roundhay at 6pm on Saturday, leaving it "completely gutted".
Police were called by the fire service and officers closed the roads.
Nearby residents were warned to stay indoors due to the potential risk from smoke from the fire.
The fire caused extensive damage throughout the building and has left it structurally unsafe.
Fire investigators have told police they think the fire was started deliberately.
Watch commander Tim Pallister said the building will now likely be demolished.
Youths had been seen in and around the site at the time leading up to the fire.
Local resident Sara Dawson, who is a member of community group Friends of Roundhay Park, said on Sunday that the building had recently attracted a raft of anti-social behaviour.Detective Inspector James Entwistle, of Leeds District CID, said: “Although the former school building is derelict, this was a major fire which required a significant emergency services response to deal with the situation and which presented potential risks to nearby residents.
"The building has been left completely gutted and unsafe as a result of the fire.
“Fire service investigators believe it was started deliberately and we are investigating the incident as arson.
“We are carrying out enquiries to identify those responsible and would like to hear from anyone with any information that could assist the investigation.
"We have had reports of youths seen in the area in the time leading up to the fire.
“We are aware the building had been a regular target for vandalism and graffiti over the years and we would urge people to stay away from the site which is obviously now very unsafe.”
Anyone with information is asked to contact Leeds District CID via 101 quoting crime reference 13210113968 or online via www.westyorkshire.police.uk/101livechat
Information can also be given anonymously to the independent charity Crimestoppers on 0800 555 111.