The big rig, which was hauling sand, crashed through the divider, hitting cars on both sides of the freeway. Authorities said one person was seriously injured in the incident.
The crash was reported at about 6 a.m. and shut down all lanes of the eastbound 101 Freeway. Traffic was at a standstill from the 405 interchange up to the accident site, just before the Hollywood Freeway interchange.
The crash also affected traffic on the westbound 101, closing two lanes of traffic.
Cars were also backed up on Riverside Drive, Ventura Boulevard and other surrounding streets, as motorists tried to take detours around the accident.
Eastbound lanes were closed for several hours as drivers used the right shoulder to pass the crash site. All lanes have since reopened.
The Associated Press contributed to this report.