At least a dozen firefighters responded to the fire on Autumn River Road South, which produced huge smoke clouds and was a risk to the structure of the home.
Two firefighters were injured in the fire, Jacksonville Fire Rescue said. They are expected to be okay.
When JFRD arrived, the fire was actively coming through the roof. Fire fighters had to be removed from the house as the house was at risk of collapse.
The homeowners were not home at the time. The State Fire Marshal has been called to investigate the cause.