The deceased motorist was identified only as a 50-year-old woman.
All northbound lanes were temporarily closed after the 4 a.m. crash, which occurred at the Third Street bridge and prompted the California Highway Patrol to issue a SigAlert. Multiple vehicles struck the vehicle after it landed on its roof, investigators said, but no other injuries were reported.
At least one lane was subsequently reopened as Los Angeles Fire Department personnel used the Jaws of Life to extricate the driver's body from the Cadillac sedan.
The cause of the crash was not immediately known.
Northbound traffic was backed up at the crash site as emergency responders and CalTrans crews conducted a cleanup operation and investigation.
The scene was cleared at 8:07 a.m., according to the CHP.
City News Service contributed to this report.