Fire and Emergency New Zealand were called to Antonio Hall on Riccarton Rd after 3.30am and found it ablaze.
Neighbours in the area were evacuated as 12 fire crews fought the blaze.
Built around 1904 for a successful grocery merchant, the grand site was purchased by the Catholic Church in 1946 as a place to educate young men entering the priesthood.
It was later used as a private hostel for students attending nearby Canterbury University and was then sold to a family who gave it its current name.
The site was badly damaged in the 2011 earthquake and has fallen further into disrepair over the past decade despite efforts from the local community to restore it.
Fire and Emergency NZ's Wayne Hamilton says it is disappointing to see another historic building go up in flames.
Last year almost a third of the mansion was destroyed when a teenager set fire to a mattress inside one of the buildings.
Since then it has been a target for vandals and thieves.
Police are investigating the fire, along with Fire and Emergency NZ.
"The investigation is in its very early stages," a police spokesperson said.
People living nearby were evacuated, but have since been allowed to return to their homes.
"All traffic cordons on Riccarton and Wharenui Rds have been removed," the police spokesperson said at 10.40am on Friday.