At least two people died, and two others were taken to the hospital with burn injuries, Deputy Fire Chief Justin Matsushita told reporters. More victims were possible, he said.
"It's a pretty brutal scene," Matsushita said.
It was also unclear whether anyone was inside the damaged homes, Garlow said. The sheriff's department was checking inside nearby homes, too, he said.
Jennifer Ward told USA TODAY she was sitting at home watching a movie when she felt the house shake.
"I thought a tree fell on my house, and then I ran outside and saw all the black smoke," Ward said. The plane crashed one street over from her. Ward said she drives down the road "several times a day."
The plane crashed between Ward's house and nearby Santana High School. Students at Santana temporarily went into secure locations and were later released.
"All the kids at the school were really scared because they didn’t know what was going on, and the school was shaking, too," said Ward, whose 15-year-old son attends Santana.
The Federal Aviation Administration and National Transportation Safety Board were investigating.
The American Red Cross of Southern California set up a temporary evacuation center at a nearby YMCA.
"We offer our deepest sympathies to the loved ones of those we lost in today's plane crash," the San Diego Sheriff's Department said on Twitter.
Santee has seen other plane crashes in recent years, Garlow said. A crash in a commercial area in 2015 killed a pilot, he said. Another crash 10 years ago in a residential area also killed a pilot, he said.
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