From there, it generally goes southeast to northwest to the East Los Angeles Interchange, where it takes the designation of U.S. Route 101 (US 101).

Formerly, the entirety of the route was marked as US 101 until the 1964 highway renumbering, which truncated US 101 to the East Los Angeles Interchange and designated the rest of the freeway as I-5.

North of the East Los Angeles Interchange complex, I-5 follows the Golden State Freeway.

An abundance of landmarks, most importantly Disneyland and Angel Stadium of Anaheim, along the Orange County portion of its route combines with a severe bottleneck beginning at the Los Angeles County line (shrinking from 10 to 6 lanes) to make it one of the most congested freeways in Southern California.

Originally it was signed as US 101 before the segment of 101 between the East Los Angeles Interchange and the United States–Mexico border in San Ysidro, California was decommissioned in favor of Interstate 5.

[17] Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.