It was organized July 10, 1880, and chartered on October 23, 1880, to build a rail connection between what has become the city of Barstow and San Diego, California.

From there, the line turned to the northeast through Temecula Canyon, then on to the present cities of Lake Elsinore, Perris and Riverside before a connection to the Southern Pacific Railroad (SP) in Colton.

The line, completed on November 9, 1885, formed the western end of Santa Fe's transcontinental railroad connection to Chicago.

Portions of the original line are still in use today as some of the busiest rail freight and passenger routes in the United States.

[2] The California Southern built its track northward from a point in National City, south of San Diego.

In Barstow, then known as Waterman, the California Southern would connect to another Santa Fe subsidiary, the Atlantic and Pacific Railroad.

The railroad's main yards and locomotive maintenance shops were located here, and until the connection was made with Barstow, all tools and equipment ordered by the railroad arrived here by ship around Cape Horn from points in the eastern United States, while the wooden ties arrived by ship from Oregon.

[9] To connect to the Atlantic and Pacific line in the quickest way possible, surveyors and engineers for the California Southern pushed the route through Fallbrook and Temecula—bypassing what was, at the time, the pueblo of Los Angeles.

Disaster was averted because a local resident, Charlie Howell, hurried up the tracks from his family homestead near Willow Glen and managed to stop the train.

[12] Temporary track repairs were made after the first storms, but later in the month, additional rains and flooding washed out the entire route through the canyon.

[17] Building north from San Bernardino, the California Southern was able to piggyback on the survey work done by the Los Angeles and Independence Railroad up to a point near Cajon.

[21] Construction of the original route through Cajon Pass was overseen by Jacob Nash Victor, who by this time had become General Manager of the California Southern.

Victor's assertion remained true for a while as the San Pedro, Los Angeles and Salt Lake Railroad (which later became part of Union Pacific Railroad) signed an agreement to operate over the California Southern track via trackage rights on April 26, 1905,[22] but Victor was proven wrong eighty years later when SP built the Palmdale Cutoff in 1967 at a slightly higher elevation through the pass.

[24] To reach Los Angeles, the Santa Fe leased trackage rights over the Southern Pacific from San Bernardino on November 29, 1885, at $1,200 per mile per year.

On November 20, 1886, the Santa Fe incorporated the San Bernardino and Los Angeles Railway to build a rail connection between its namesake cities.

California Southern track crews performed the construction work, and the first train on the new line arrived in Los Angeles on May 31, 1887.

During construction, Santa Fe officials worked to consolidate the many subsidiary railroads in Southern California to reduce costs.

At Cajon, the concrete pads that served as the foundations for the railroad's station facilities and water tanks there remain long after the buildings atop them were removed.

The Santa Fe realigned the track at several places during the 20th century to straighten curves along Cajon Creek (between Cajon and San Bernardino), lower grades for eastbound trains with the 1913 addition of a separate track through what has come to be known as Sullivan's Curve, and to reduce some curvature and lower the pass's summit elevation by 50 ft (15 m).

At the southern end the section between San Diego and Oceanside also sees heavy use by Amtrak California's Pacific Surfliner trains as well as those of the Coaster.