It happened around 12:30 a.m. in the 7900 block of St. Louis Street at the corner of Fleta Drive in the Settegast neighborhood.
Houston firefighters were able to bring the fire under control before it could spread to nearby homes.
Arson investigators were looking into the cause because it was the second fire within a few blocks in about an hour's time.
The vacant building was once home to the Truevine Baptist Church, according to a sign in front of the property.
No injuries were reported. The building is considered a total loss.
RELATED: Massive fire destroys 100-year-old church in Rosharon