Firefighters responded to the home in the 4400 block of Cobble Creek in the Winchester neighborhood of Northeast Raleigh just before 5 p.m.
The flames caused major damage to the roof and second floor of the home.
No one was at home when the blaze started.
One firefighter received minor injuries and was taken to the hospital as a precaution.
The home was a total loss.
Lightning was blamed for sparking two other fires in Raleigh Wednesday evening.