It was named after Major General Joseph Henry Pendleton (1860–1942), who had long advocated setting up a training base for the Marine Corps on the West Coast.

In 1769, a Spanish expedition led by Captain Gaspar de Portolá explored northward from Loreto, Baja California Sur, seeking to reach Monterey Bay, something never before done overland by Europeans.

On July 20 of that year, the expedition arrived in the area now known as Camp Pendleton, and as it was the feast day of St. Margaret, they christened the land in the name of Santa Margarita.

More land was later added to the grant, giving it the name of Rancho Santa Margarita y Las Flores, which stayed with the ranch until the Marine Corps acquired it in 1942.

It was purchased by wealthy cattleman James Clair Flood and managed by Irishman Richard O'Neill, who was eventually rewarded for his faithful service with half ownership.

Under the guidance of O'Neill's son, Jerome, the ranch made a profit of nearly half a million dollars annually, and the house was modernized and refurbished.

The Army lost interest in the project, but in February 1942 it was announced that the 122,798 acres (497 km2) of Rancho Santa Margarita y Las Flores would be transformed into the largest Marine Corps base in the country.

[3] It was named for Major General Joseph Henry Pendleton who had long advocated the establishment of a West Coast training base.

When Camp Pendleton trained the country's fighting force for the Korean and Vietnam Wars, approximately 200,000 Marines passed through the base on their way to the Far East.

[7] The camp's stables display a plaque and statue commemorating a horse, Sergeant Reckless, which served with the Marine Corps in Korea.

Camp Pendleton remains the last major undeveloped portion of the California coastline south of Santa Barbara, save for a few relatively small state parks.

[12] Since August 2004, Camp Pendleton has been one of five locations in the Department of Defense to operate the Standard Terminal Automation Replacement System (STARS) air radar.

Among the more famous performers who were accompanied by the Camp Pendleton color guard have been Frankie Laine, Herb Alpert, Wilson Phillips, Jewel, Trisha Yearwood and the Dixie Chicks, all of whom had performed the National Anthem at either a World Series game, Super Bowl, or, in Wilson Phillips' case, a Major League Baseball All-Star Game that was played at what is now SDCCU Stadium.

It will also result in additional losses of natural areas that support endangered species, thus placing an even greater burden on Camp Pendleton to protect the region’s biodiversity.”[14] In 2008, after the rejection of the proposed toll road extension of SR 241 through San Onofre State Beach Park for environmental reasons, the TCA filed for permission to build on the northwestern portion of the base.

[15] The TCA funded a study in 2013 to remove the California gnatcatcher from the endangered species list, which would have made it easier to negotiate the construction and planning of the 241's extension through the San Onofre State Beach Park.

Camp Pendleton was built on a wide swath of coastal land that once supported an estuary at the mouth of the Santa Margarita River and extensive salt marsh habitat.