Archaeological evidence shows that the island was inhabited, at least on a seasonal basis, by Indians, perhaps as a result of population growth on larger neighboring islands such as Santa Catalina. Due to the lack of firewood, water and basic subsistence materials, this island would be less desirable than some of the others. Given this islands central location, it may have served as an important stop over point for inter-island travel. The Gabrielino Indians spoke a Shoshonian dialect and inhabited the Southern Channel Islands and adjacent mainland.

In 1542 Juan Rodriguez Cabrillo, a portuguese sailor, set sail from Navidad, Mexico with the purpose of exploring the west coast of New Spain. He was the first European visitor to the Channel Islands. He made no mention of the island.

In 1602 Sebastian Vizcaino, a Spaniard, sailed the west coast of California. He bestowed the name Santa Barbara on the channel after the martyred Roman virgin whose feast day was December 4th, a day which found him anchored off the mainland coast. Vizcaino also gave the name to the easternmost of the Anacapa Islands but it was not until 1793 that George Vancouver, an english explorer, finalized the names of the eight Channel Islands.

In 1821 Santa Barbara Island became a possession of Mexico after a successful revolt from Spain and with California statehood in 1850, unclaimed and uninhabited Santa Barbara Island changed ownership from the Mexican government to the United States. Shortly thereafter, a U.S. Coast Survey team visited Santa Barbara Island, and in 1871 a survey station point was established atop the islands highest point, Signal Peak. For the remainder of the 19th century, this small oceanic outpost was occupied seasonally by fisherman, transient seal hunters and Chinese lobster trappers. In the 1890s, H. Bay Webster, lessee of Anacapa Island, built a cabin on a Santa Barbara Island promontory which today bears his name. In 1909, the island was officially leased by the U.S. government to J.G. Howland for $26 a year for five years. Although his lease forbade subletting, Howland sold fishing rights to Japanese and Chinese fisherman, and rented island space to an abalone pearl propagation business.

In 1914 when the Howland lease expired, Alvin Hyder of San Pedro, California became the second lessee, paying $250 for his five year lease. The subsequent development of Santa Barbara Island became an extended Hyder family affair. Alvin Hyder and his wife and two children were soon joined on the island by Alvin's two brothers, Clarence and Cleve, and their respective families. As many as 17 people lived on this small island which provided no fresh water and little protection from the weather.

To eke out a living on Santa Barbara Island, the Hyders imported horses, mules, rabbits, ducks, geese, turkeys and chickens. Time and again chickens were blown out to sea before they could be cooped at the onset of high winds. The raising of sheep for wool and meat became the mainstay of Hyder operations. Building materials, supplies, water and livestock were hauled to the island by Alvin aboard his boat, Nora, To supplement the family income, he hauled animals and supplies to and from the other islands. During the "dry years" of Prohibition, Alvin Hyder was well known for his prowess and agility in rum-running the length of the Southern California coast.

In 1919 after the Hyder lease expired, Santa Barbara Island was again advertised by the government for lease to the highest bidder. Alvin Hyder was outbid by Abbot Kinney of the Venice Chamber of Commerce who bid $1250. Kinney dreamed of a public camping and fishing development. The Hyders however were determined to remain on the island. In 1920, Kinney failed to pay his lessee fee, and his lease was revoked. It was not until 1922, after nine years of stubborn determination followed by failure, that the Hyders packed their things and moved to the mainland.

In 1929 a navigational light was installed on the northwest corner of the island. The unmanned acetylene lantern equipped with a flasher was installed on a white wooden pyramid 190 feet above sea level. It protected shipping along the Hawaiian Island and Trans-Pacific route which follows a course six miles north of the island. This light remained in service until 1986 when a solar powered battery operated light was installed.

From 1942 through 1946 the island served as a military outpost and a point of early warning against a possible Japanese attack. Miscellaneous buildings, barracks a a boat landing facility were constructed.Motor vehicles and dirt roadways appeared during this occupation. In the 1960s, a photo-tracking station was set on the island by the Navy until it was turned over the the National Park Service. Today the site serves as housing for the National Park Service staff and as a small visitor center.

In 1993 the Santa Cruz Island Foundation sponsored a small museum on Santa Barbara Island in Channel Island National Park facilities.