The crash happened on the runway shortly before 5 p.m., according to Sgt. Adam Gwartz with the Santa Monica Police Department.
"There was a fire," Gwartz said. "The plane did not hit any structures."
TV news footage showed the charred wreckage of an aircraft on the tarmac with multiple fire trucks at the scene.
There were two people aboard and both were killed, the Santa Monica Fire Department said on Twitter.
The plane was a Piper Sport, the Federal Aviation Administration said. The FAA and the National Transportation Safety Board will investigate.
The airport’s single runway sits amid residential neighborhoods in the city of more than 90,000 on the Pacific Ocean. City leaders and many residents advocate closing the airport, citing noise and safety concerns.