Police confirmed the fire, which largely destroyed the 123-year-old St James Church in Brighton on Monday morning, was being treated as suspicious.

Fairfax Media understands detectives are now investigating if the fire is linked to the crimes of Ronald Pickering, who served as the church's parish priest from 1978 to 1993 before he fled to the United Kingdom, fearing prosecution.

At least five people killed themselves after being sexually abused by Pickering between 1960 and 1980, according to research by Monash University's law faculty. Pickering died in 2012.

Screen star Rachel Griffiths, who made her first communion at St James, said to see the church smoking was "a relief".

"I think its always been a difficult building for us to drive past, because there's so much tragedy and complicated feelings," she told radio station ABC 774 on Monday.

"We've all attended funerals of boys that we now know were abused by Pickering.

"We've all avoided being married there and found other churches, and it's kind of been a bit of a thorn to see it standing."

Emergency services were called to the church on North Road about 6.30am after neighbours reported hearing a loud bang and saw smoke coming from the church.

Upwards of 60 firefighters fought the blaze, bringing it under control shortly after 7.30am.

They prevented embers from impacting nearby homes and the school behind it, but the intensity of the fire caused the pine roof to collapse. The interior was destroyed.

Detectives are now asking for anyone who may have seen anything suspicious in the area to come forward.

As of yesterday afternoon, arson chemists were yet to determine how the fire started.

The church's new priest, Reverend Michel Corriveau, did not speak publicly on Monday.

Catholic Archdiocese of Melbourne's communicators director, Shane Healy, said they were awaiting the results of the police investigation.

He said he did not know if the fire was linked to Pickering.

"There could be people out there - if it's been done deliberately - who could have any sort of motive," he said.

Mr Healy said Reverend Corriveau, who arrived at the church at the start of the month, and parishioners were "very, very upset".

"It really was the living, breathing heart of the early church in Melbourne," Mr Healy said.

They hoped the facade of the church could be saved.

Other resident were devastated to see their local church all but destroyed, with life-long parishioner Bob McEwan reflecting on the significant  events he had experienced there, including his mother's funeral two years ago.

"My auntie had her funeral only two weeks ago, so there's a huge emotional and spiritual attachment to it," Mr McEwan said. "It's a magnificent church."

Annie O'Donoghue was another local who had a long history at St James and woke on Monday to flames billowing from its roof.

"We got married here, my husband grew up in the parish, and our five children have been baptised here," she said.

Mrs O'Donoghue said  of Mr Corriveau: "When he started, he was so enthusiastic, everyone was really excited.

"For this to happen, he's got his job cut out for him now."

The fire happened in the lead-up to one of the busiest times of year for the parish, with its Easter services usually attracting thousands.

Mr Healy said services would be moved to the Star of the Sea chapel next door.

It was "too early" to tell whether insurance would cover the damage bill, which was still unknown.

Chris MacIsaac, president of church abuse victims' advocacy group Broken Rites, said it was it tragic to see the building burnt out despite the sordid history of abuse there.

"It's sad really, it's sad to lose such an iconic building," Ms MacIsaac said.

The Catholic church dates back to 1892, and a small wooden church stood in the same spot for at least 10 years before that, according to the church's website.

It was heritage listed as a building of state significance in 1984.

Monday's fire comes after the historic Rupertswood Mansion, also the site of alleged routine abuse by priests, narrowly avoided being burnt down in August last year.

A school bus was set alight on the mansion lawns with fire crews preventing its spread. No one has been charged.