It runs from State Route 1 (SR 1) near El Segundo and Los Angeles International Airport (LAX) to Studebaker Road in the City of Norwalk.

A portion of undeveloped land south of this section of Imperial Highway exists to facilitate a potential extension of the freeway.

Upon reaching the Harbor Gateway neighborhood of Los Angeles, I-105 intersects with I-110 at the five-level Judge Harry Pregerson Interchange.

2 mi (3.2 km) from the western end of the freeway, the C Line separates onto its own right-of-way at Aviation Boulevard before turning north towards the LAX area, where a future people mover connecting Metro Rail to airport terminals is scheduled to open in 2026.

Fiscal difficulties brought about by the 1971 Sylmar earthquake and the California tax revolt of the late 1970s further hampered Caltrans' construction efforts.

Most cities along the way, weary of the noise and visual blight created by elevated freeways, demanded that the route be built far below grade in a "trench".

[citation needed] In 1972, community opposition resulted in a federal lawsuit, Keith v. Volpe, being filed, charging a violation of various civil rights protections and the National Environmental Policy Act (NEPA).

In 1979, this lawsuit resulted in a Consent Decree, amended in 1981, which imposed several conditions on the development of the freeway, including additional public hearings, preparation of an environmental report, alterations to the design to reduce lanes and intersections, improve carpooling and provide for a transitway, which became the Los Angeles Metro Rail Green Line, now known as the C Line.

After construction began in the 1980s, failure to perform a complete survey of the area's groundwater deposits, combined with the 20–30-foot (6.1–9.1 m) below-grade trench through the city of Downey, resulted in buckling and cracking along the eastern portions of the route.

The childhood home of Brian, Carl and Dennis Wilson of the Beach Boys was demolished in the mid-1980s to make way for the freeway, as was the house across the street where their bandmate David Marks grew up.

Throughout the difficulties, Congressman Glenn M. Anderson (D-San Pedro) tirelessly advocated for the route's construction, making claims it would provide congestion relief along Century, Manchester, and Firestone Boulevards and the Imperial Highway, as well as relieving pressure on the Santa Monica (I-10) and San Diego (I-405) Freeways for travelers between Downtown Los Angeles and LAX.