The fire at the two-story structure was first reported shortly after 5 a.m. in the 10800 block of S. Broadway Street, according to the Los Angeles Fire Department.
The address came back to Greater New Holy Trinity Missionary Baptist Church.
Responding firefighters found flames coming from the second floor, the department said. Crews operated in defensive mode.
Video from AIR7 showed that part of the roof had collapsed.
The fire was declared a knockdown just after 7 a.m. Crews remained on scene to mop up, LAFD said. Arson investigators were called to the scene, per protocol. No injuries were reported.
Broadway Street was closed in both directions in the area. Drivers were advised to use alternate routes.
The building was vacant at the time of the fire, fire officials said. They added that there was construction happening on the building. No injuries were reported.
An area resident who used to attend Greater New Holy Trinity said the church has been closed for years.
"This is the second time we had that. It has been vacant for probably six years, seven years, and then the homeless moved in," he said.
LAFD says the Los Angeles Department of Building and Safety is assessing the heavily damaged church building "to ensure viability and structural integrity."
The cause of the fire is under investigation.