Emergency crews work at the scene of a small plane crash in Santee, California, on Monday. AP

A twin-engine plane crashed blocks from a high school campus near San Diego on Monday, killing at least two people and left a swathe of destruction after repeated warnings that it was flying dangerously low, according to a recording.

Officials and local media said at least two homes appeared to have been destroyed by an ensuing fire in the city of Santee, California, where the crash occurred.

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"At approximately 12pm today, a small twin engine plane crashed into two residential homes in Santee," the tweet added.

Fire crews work at the scene of a small plane crash in Santee, California, on Monday. AP

The C340 smashed into a UPS van, killing the driver, and then hit houses just after noon on Monday in Santee, a suburb of 50,000 people. The pilot also is believed to have died, and at least two people on the ground were hurt, including a woman who was helped out the window of a burning home by neighbours.

Several vehicles were burned, but firefighters were able to put out the blaze before it spread to other houses. Two deaths were confirmed and two other people were taken to a hospital.

Santana High School, located three blocks from the crash, said on Twitter that all its students were "secure."

A fire official looks over the scene of a small plane crash in Santee, California, on Monday. AP

The plane was owned by Dr. Sugata Das, who may have been piloting the aircraft and died in the crash.

He worked at Yuma Regional Medical Center in Arizona, the hospital's chief medical officer said.

Das, a licensed pilot, lived in San Diego and commuted back and forth to Yuma, according to a website for a non-profit organization he served as director. He leaves behind two young sons.