The fire, which police believe was started deliberately, broke out at around 3pm on Saturday at the old St Mary's boys' Home in Boston Spa, near Wetherby.
West Yorkshire Fire and Rescue service sent five engines to the building on Church Street after being alerted to the fire by residents.
It spread to all three floors of the building causing substantial damage.
A fire investigation team found signs of forced entry into the building and suspected deliberate ignition.
No one was inside the building when firefighters arrived and no crews were injured.
The fire was extinguished and crews left the building on Saturday evening.
A fire spokesperson told the Yorkshire Evening Post: "Crews were called at 3pm in the afternoon after we were alerted by residents.
"The incident, at its height, had five engines from Wetherby, Moortown, Killingbeck and Tadcaster.
“Given the change of shift at 7pm, this was supplemented by additional crews from the same stations.
“The fire involved all three floors - the ground, first and second - causing substantial damage throughout.
"No firefighters were injured.
“There were signs of forced entry, but no persons were involved and no injuries.
“It is suspected deliberate ignition and police and the fire investigation team working together to investigate the cause."