Fishergate was closed as the eight fire engines and and two aerial ladder platforms tackled the blaze at the derelict St Joseph’s Orphanage on Mount Street.
The fire was under control as of 10pm with crews set to be on the scene long into the night. No injuries have been reported.
The fire started on the third floor, spreading to the roof, with an initial four engines at the incident quickly extended to eight, due to the smoke and spread of the fire.
The two aerial ladder platforms were needed due to the height of the incident.
Lancashire Police and the North West Ambulance Service are on the scene supporting Lancashire Fire and Rescue Service, as are building surveyors.
It is understood some demolition work at the site was due to start on Monday.
Group manager Tom Cookson, acting as the incident commander, told the Lancashire Post: “Currently our fire fighting tactics have been successful and the fire in the roof and on the third floor is under control.
“Further assessments are being made. The building is not of sound structural integrity, therefore firefighters are not entering the building and all our operations are being completed externally.
“It’s envisaged the fire service will be at the incident for several hours to come and there will be appliances here throughout the night for dampening down operations.
“There’s been no injuries.”