The fixed-wing aircraft went down just before 12:30 p.m. near Hubbard Street, resulting in a small fuel leak that did not ignite a fire, the LAFD said.
A statement issued by the Federal Aviation Administration said the pilot was the only person aboard the twin-engine Cessna 337 Skymaster.
The identity of the pilot was not immediately released.
"After a thorough search of all void spaces in the aircraft, firefighters did not locate any other victims," the news release said.
Northbound traffic on the freeway was backed up at the scene as more than a dozen Urban Search and Rescue firefighters sifted through the wreckage.
The plane's destination and the cause of the crash were unknown.
The FAA and the National Transportation Safety Board are continuing their investigation.