The crash was reported around 11 p.m. Sunday near the Riverside Drive exit. According to the Los Angeles Police Department, the driver appears to have lost control, hit the curb and then crashed through the overpass fence before landing on the freeway.
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The car crashed into the concrete center divider on the freeway and caught fire.
Two men in their 60s were able to get out of the car before it exploded in flames. They were hospitalized in serious condition but are expected to survive.
Authorities said there were no signs of driving under the influence. A cause for the crash has not been determined, but police say it appears the driver simply lost control of the vehicle.
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Hours after the crash, the eastbound side of the freeway was open and clear, while all but one lane of the westbound side remained shut down during the clean-up.