It happened just after 11 pm Sunday on Mendocino Avenue near Rose Avenue, between Selma and Reedley.
Fresno County Sheriff's deputies say a man in his 50s and a woman in her 40s parked a U-Haul truck at the home and began stealing property.
The homeowners arrived, spotted the truck and called 9-1-1.
The thieves are then accused of lighting a fire inside the home before driving off in the U-Haul.
Deputies found and arrested the pair a few blocks away.
The fire destroyed the home's second story, and the residents will need to find another place to stay.
A GoFundMe has been started to help the family.