Witnesses described a retired couple being rescued from one of two homes that were destroyed in Santee, a largely residential suburb of 50,000 people. Ten other homes were damaged.
Several vehicles, including a UPS delivery truck, were also torched.
"Not to be too graphic, but it's a pretty brutal scene," Justin Matsushita, Santee's deputy fire chief, said as firefighters searched the smoldering ruins.
United Parcel Service of America Inc confirmed one of its workers died.
"We are heartbroken by the loss of our employee, and extend our deepest condolences to his family and friends," the company said. "We also send our condolences for the other individuals who are involved in this incident, and their families and friends."
The condition of the two injured wasn't immediately known.
Michael Keeley 43, ran barefoot outside when his home shook. He saw the UPS truck in flames and found two neighbors at a burning home calling through an open window.
With thick smoke inside the neighbours' home and flames licking the roof, Keeley stood on a rock and reached through to grab the woman's arm and help her climb out of the window. Her forearms were burned, and her hair was singed.
"She kept saying, `My puppy, my puppy,"' Keeley said.
The plane was a twin-engine Cessna C340, according to the Federal Aviation Administration.
It was believed to be a private aircraft flying from Yuma, Arizona, to Montgomery-Gibbs Executive Airport in San Diego, Matsushita said. It was unknown how many were on board, but Mastushita said no one would have survived.
The crash site is a few miles north of Gillespie Field, a small San Diego County airport.
The FAA and the National Transportation Safety Board will investigate.
