Vandenberg AFB began in the summer of 1941 as Camp Cooke, an Army training site for rapid artillery and armor training. The Camp Cooke location, in a relatively remote section of central-southern-coastal California, was considered ideal for shelling and gun practice, and was large enough to allow fast maneuvering, away from observing populations, which could be safety and security problems. The camp was named for Major General Philip St. George Cooke, the "Father of U.S. Cavalry" and a veteran of forty-six years of US military service, from before the Mexican-American War to after the Civil War.

World War Two came on the US only two months after the first Army unit, the 5th Armored, rolled into Camp Cooke. Over the course of the war the 5th, 6th, 11th, 13th, and 20th Armored Divisions, the 86th and 97th Infantry Divisions, the 50th Armored Infantry, and the 2d Filipino Infantry Regiment all trained at Camp Cooke, as did as various anti-aircraft artillery, combat engineer, ordnance, and hospital units, most of which served in the European theater. Camp Cooke also separately housed German and Italian Prisoners of War; after the Italian surrender in 1943, the Italian POWs worked in needed non-vital support roles, including repair, clerical work, laundry, and food service. The German POWs also worked in local agricultural labor, relieving a local labor shortage - many of the laborers having gone to war. Camp Cooke's activity level dropped after the end of the war, and a maximum security disciplinary barracks was constructed on site; the prisoners were assigned the duty of caretaking the camp, which was otherwise closed and leased for grazing.

In 1950 Camp Cooke became a training site for the 40th and 44th Infantry Divisions, preparing for duty in the Korean War. The camp was also used for Army National Guard training, then again closed. The discipline barracks remained active this entire period, until 1959, when it transferred to the US Federal Bureau of Prisons.

In 1956, the US Air Force, expanding facilities in support of its space programs, selected Camp Cooke as a site for what would become the Western Range. This section of California was isolated, relatively easy to secure, ideal for year-round operations, and could support rocket launches without overflying civilian population; basically, the same reasons the Army had selected the site.

In 1957 northern Camp Cooke was transferred to the Air Force and named Cooke Air Force Base. Much of the original, World War Two era, camp was torn down; the rest required intensive renovation. For two years the base underwent upgrading to mission requirements, including road repair and paving, runways, launch pads, concrete buildings, hangars, military barracks and family housing. As the new base was being built, the US space program was developing rapidly, and even more rapidly once the Soviet Union launched Sputnik in October 1957. In 1958 south Camp Cooke was transferred to the US Navy, for their missile development and testing program. Also in 1958 Cooke AFB was renamed Vandenberg Air Force Base, to honor General Hoyt S. Vandenberg, highly decorated World War Two Army Air Force veteran, commander of the Ninth Air Force (among many other achievements in the war), former Director of the CIA, and Chief of Staff of the Air Force, who died in 1954.

Vandenberg AFB and units was under command of Strategic Air Command, with a mission of supporting the ballistic missile military requirements of the Air Force, and developing rockets for space launch. The first launch from Vandenberg AFB was a Thor Intermediate Range Ballistic Mission, in December 1958. Less than a year later, September 1959, the first Intercontinental Ballistic Missile, an Atlas D, was successfully launched. These launches were important early steps to the development of the US ballistic missile arsenal and the US space program. The Atlas was the rocket used in Project Mercury, launching Alan Shepard to become the first American in space, and John Glenn, the American in orbit. The Atlas rocket series proved to be a reliable rocket, and are still used for satellite launches.

In February 1959 Vandenberg launched the first polar-orbit satellite, Discoverer I. The Discoverer launch program also saw the first object recovery from space (Discoverer XIII) and the first air recovery of an object from space (Discoverer XIV). It also served as a cover for Corona, the first satellite photo reconnaissance program; Discoverer XIII was the first orbital imaging mission, having successfully returned photographic film from space.

The 1960s was a period of rapid development for US missile and rocket systems. The early ICBM missiles, the Titan and Atlas families, were cycled out as military launchers, and the highly successful Minuteman series was developed and deployed. The space race with the Soviet Union was continuing to speed up, and the earliest manned satellites and space shuttle concepts were being designed.

As the 1970s dawned, the space program seemed to be going well; man had visited the moon, and the space shuttle program and a manned space station was being planned. Vandenberg AFB was selected as the West Coast launch site for the space shuttle, with Edwards AFB designated the shuttle landing strip for easy relocation to Vandenberg, but by the mid-1970s budget cuts restricted these programs and the shuttle never launched from Vandenberg.
The 1980s brought a general shift of the space program to Florida space facilities; Vandenberg began to focus on the longer range Peacekeeper ICBM system and satellite launches. The Peacekeeper was successfully launched in 1983, and the satellite launch program proceeded successfully.

The 1990s and 2000s have seen the development of Vandenberg launch facilities into a launchpad for commercial satellites and other private space ventures, including the California Spaceport, the SpaceX private space program, which has recently become a carrier for supplies to the International Space Station.