The two-car collision happened on the southbound side of the 5 near the 210 Freeway interchange, according to the Los Angeles Fire Department.
The unidentified woman was pronounced dead at the scene, fire officials said. An 8-year-old, one of three children in the same vehicle as the woman, was transported to a hospital in critical condition. The two other children were hospitalized in fair condition.
The occupants of the second vehicle were uninjured, according to a spokesperson for the California Highway Patrol.
The cause of the crash was under investigation.