The NYPD Hate Crime Task Force is investigating the blaze, which broke out at about 5:30 a.m. at the convent at St. Joseph Academy on Hylan Boulevard in the Arrochar section.
Timothy Cardinal Dolan celebrated mass there Sunday as part of a previously planned event to mark the 100th anniversary of the Daughters of Divine Charity.
Six people were injured in the fire, including four firefighters and two nuns.
As firefighters raced to help, Eyewitness News is told sister Regina jumped out of the window to the unforgiving concrete below, breaking three vertebrae in her spine. She was taken to Staten Island University Hospital.
Cardinal Dolan went to the hospital after the homily to be with sister Regina, who remains in ICU.
"When you look back at their history, you see that they've had difficulties and challenges all along for the last century," said Dolan. "And all the time, instead of surrendering they keep going and they're stronger than ever."
The second nun was treated at the scene.
When firefighters arrived they spotted people at the windows, and flames on both the first and third floors.
Over 100 firefighters responded to the scene, and managed to extinguish the fire within a half hour.
"The historic portion of our home, with our chapel, sacristy, archives and provincial offices was destroyed and is now a crime scene," said Sister M. William McGovern, the Provincial Supervisor. "We will rebuild, we will restore our Convent and our place of worship."
Sister M. William McGovern is convinced the fire was a hate crime.
Photos obtained exclusively by Eyewitness News show the scope of the damage at St. Joseph Hill Academy.
She says what you cannot see is a religious statue that was beheaded near the altar.
NYPD officers are now guarding the compound.
The newly-built convent was vandalized in August 2013, just days before construction was completed.
The convent is on the grounds of St. Joseph Hill Academy, a 14-acre Catholic school for kindergarten through the 12th grade.
Investigators are now looking to see if the vandalism this summer is in any way connected to this weekend's devastating blaze.