North of I-10, the freeway continues as SR 110 through Downtown Los Angeles to its junction with US 101 at the Four Level Interchange.

Its interchange with the Santa Monica Freeway is notoriously busy and congested, and the portions bordering Bunker Hill in northwest Downtown Los Angeles are choked with traffic at peak travel times.

Of particular note is the Judge Harry Pregerson Interchange, which contains the most elaborate network of direct HOV/HOT connectors in Los Angeles County.

It includes a seven-story ramp that connects the Century Freeway's HOV lanes to the Harbor Freeway's northbound HOT lanes and offers splendid views of the entire Los Angeles Basin and the San Gabriel Mountains.

The Harbor Transitway is a grade-separated, shared-use express bus and high-occupancy toll (HOT) corridor, running in the median of I-110, between SR 91 (Gardena Freeway) and Adams Boulevard in the south side of Downtown Los Angeles.

The southern end of the HOT lanes also includes dedicated ramps connecting to the Harbor Gateway Transit Center.

Solo drivers are tolled using a congestion pricing system based on the real-time levels of traffic.

[26] (The Arroyo Seco Parkway was completed to the Four Level Interchange on September 22, 1953, and renamed the Pasadena Freeway on November 16, 1954.

[37] There it connected with a section that had been open since June 19, 1956, from Pacific Coast Highway south to Channel Street.

[38] Along with the Vincent Thomas Bridge to Terminal Island, the final piece in San Pedro opened on July 9, 1970, completing the Harbor Freeway to its present length.

[43] Prior to Ankrom's work, the only signage directing motorists to the I-5 North off-ramp came at a quarter-mile (0.4 km) before the exit, thus forcing many to merge across multiple lanes in a very short distance.

Instead, Caltrans has pushed for a protected status alternative to preserve the Arroyo Seco Parkway as a historic landmark.

The state legislature designated the original section, north of the Figueroa Street Viaduct, as a "California Historic Parkway" (part of the State Scenic Highway System reserved for freeways built before 1945) in 1993;[47] the only other highway so designated is the Cabrillo Freeway (SR 163) in San Diego.