Crews went to the home on Hughes near Highway 180 after a driver in the area spotted smoke and called 911.
Firefighters were told as many as five people may be inside, so they started a potential rescue. They later learned no one was home.
A battalion chief at the scene tells Action News it appears the fire started in a bathroom, and then smoke spread into the attic and subfloor of the house.
"It is a suspicious fire right now because the first witnesses stated they saw a window open and it just happens to be on the side where the fire started," Fresno City Fire Battalion Chief Tony Escobedo said.
Firefighters say the house has a significant amount of smoke damage,