It happened around 6:15 a.m. in the 1000 block of Terminal Street in east Houston.
More than a dozen units responded to the structure near the corner of Terminal Street and Avenue J in the Greater East End.
The home is located in a neighborhood adjacent to Union Pacific Railroad tracks and is a wood frame structure.
Flames from the home could be seen for miles as Skyeye flew over the scene Wednesday morning.
A 40-year-old man suffered smoke inhalation.
The fire may have started from an electrical issue, fire officials said.
A man living at the home tried to reset an electrical breaker that had tripped and later heard a loud noise, according to HFD.