The Red Cross is helping two residents of the building at 618 Baker St. find alternative housing and firefighters remain at the scene, a Fire Department dispatcher said.
The two injured men are being treated for serious burns.
Firefighters were called to the blaze at 8:52 p.m. on Baker between Fulton and McAllister streets.
The conditions of the two injured victims are not yet known, according to the Fire Department.
A neighbor said the homeowners had just finished over two years of renovations on the home.
Arson investigators are at the scene trying to determine the cause of the fire.
ABC7 News contributed to this report.