I-5 links the major California cities of San Diego, Santa Ana, Los Angeles, Stockton, Sacramento, and Redding.

[7] The segment of I-5 from State Route 89 (SR 89) to US 97 forms part of the Volcanic Legacy Scenic Byway, an All-American Road.

I-5 itself continues northwest and meets the western end of SR 905, a route that connects with the Otay Mesa border crossing.

I-5 then continues northward and joins the southern end of SR 75, a highway connecting to Coronado via the Silver Strand.

It continues along the east side of San Diego Bay where it intersects with SR 54 and enters National City.

In addition to serving downtown San Diego, I-5 also provides access to Balboa Park from the Pershing Drive exit.

[13] I-5 continues northwest from downtown as the San Diego Freeway[14] until it reaches its junction with I-8, then turns slightly to the north while passing SeaWorld and Mission Bay.

[17] After crossing the county line, I-5 goes through several cities southeast of Los Angeles, including La Mirada, Santa Fe Springs, and Norwalk.

In Downey, I-5 intersects I-605, which serves as a north–south connector route between the cities east of Los Angeles, including those in the San Gabriel Valley.

I-5 continues along the western city limits of Santa Clarita and passes Six Flags Magic Mountain, intersecting SR 126 just north of there.

The Golden State Freeway then rises sharply, passing by Lake Castaic and undergoing a unique crossover resulting in a left-driving configuration for about 5 mi (8.0 km) before the highway crosses back into its standard alignment.

[25][26] An automated gate on the freeway's median in Castaic north of Lake Hughes Road allows drivers to turn around when such closures occur.

I-5 parallels SR 33, skirting along the far more remote western edge of the Central Valley, and is largely removed from the major population centers such as Bakersfield, Fresno and Modesto; other state highways provide connections.

I-5 still runs within the vicinity of Avenal, Coalinga, Los Banos, and a handful of other smaller cities on the western edge of the Central Valley.

I-5 passes through the western portion of the Lodi city limits before intersecting SR 12 and entering Sacramento County.

[29] I-5 enters the city of Elk Grove while passing along the eastern edge of the Stone Lakes National Wildlife Refuge.

In California, the former western branch of Interstate 5 (the northern end of the spur into the Bay Area) connecting I-80 out of Vacaville to near Dunnigan, previously known as I-5W, was renamed I-505.

"[34][35] A widowed Edendale resident, Lomie Puckett, resisted the condemnation of one of her rental properties in August 1958 by using a rifle to threaten state workers and police.

Due to high traffic demand, the freeway started undergoing major extensions and widening in the early 1990s in Orange County.

At the turn of the century, it was the most direct automobile route between Los Angeles and the San Joaquin Valley via the Mojave Desert and Tehachapi Pass.

Additionally, by 1930, a bypass road was constructed to avoid Newhall Pass via Weldon and Gavin canyons, which is the current route of I-5.

As a result of the 1994 collapse, this interchange was renamed the "Clarence Wayne Dean Memorial Interchange", honoring a Los Angeles Police Department motorcycle officer killed when he was unable to stop in time and drove off the collapsed flyover ramp from SR 14 south to I-5 south.

To prevent head-on collisions, the two ends of the route were separated on two different mountainsides, and the section through Piru Canyon was moved to an entirely new alignment to make room for Pyramid Lake.

[45] The median on I-5 between Wheeler Ridge and Tracy is wide enough to accommodate widening the West Side Freeway to six or eight lanes, should the need arise.

An intricate drainage system, water pump and retaining wall are used to protect the freeway from the Sacramento River.

[49] The carpool lane expansion from Lomas Santa Fe Drive to SR 78 fully opened by late 2023.

In 2013, ground broke on a major expansion of the freeway through La Mirada and Norwalk in neighboring Los Angeles County to the I-605 interchange, which included a carpool lane to Florence Avenue.

OCTA and Caltrans are expected to work with the residents of San Clemente during the process, as several bridges may have to be replaced with wider ones, and buildings may have to be demolished for the widening.

North of downtown Los Angeles, the freeway is currently going widening, which includes the addition of HOV lanes in four phases.

[54] The fourth and final phase is in the Santa Clarita Valley, where Caltrans is undergoing construction to extend the carpool lane from the Newhall Pass interchange to Parker Road in Castaic.