The society's origins trace to 1936, when Howard S.F. Randolph, a historian and genealogist from New England, arrived in La Jolla and grew fascinated by the community's early development. Working with the Library Association of La Jolla, now the Athenaeum Music and Arts Library, he gathered photographs and documents, eventually publishing La Jolla: Year by Year in 1946. That book sparked local interest in preservation, and Randolph's collection became the foundation for the archives the society maintains today. By the 1960s, a land boom was transforming La Jolla. Beach cottages fell to bulldozers, replaced by high-rises and modern commercial buildings. The arrival of UC San Diego and the Salk Institute changed the community's character. Concerned citizens realized they needed a dedicated organization, and on July 7, 1964, they filed articles of incorporation for the La Jolla Historical Society.

Wisteria Cottage was built in 1904 and soon acquired by Virginia Scripps, half-sister of Ellen Browning Scripps. Between 1907 and 1909, architect Irving J. Gill made additions including the wisteria-covered pergola that gives the cottage its name. By 1916, it had become part of a Scripps family compound that included South Molton Villa, now the Museum of Contemporary Art San Diego. The cottage's later life was equally eclectic: from the 1940s through the 1960s, it housed the Balmer School, an elementary school that grew into La Jolla Country Day School. From the mid-1960s to 2005, it served as a bookshop, first as Nexxus Bookstore, then as John Cole's Book Shop. In 2008, Ellen Clark Revelle, great-niece of Ellen Browning Scripps, bequeathed the property to the society. After restoration, Wisteria Cottage reopened in 2014 as a museum and exhibition space.

The campus includes several other structures, each with its own rescue story. The 1909 cottage, saved from demolition through the efforts of La Jolla developer Dewhurst and Associates and the Revelle family, now serves as offices and research space with its original wainscoting, wavy glass windows, and pine plank floors. The 1917 Carriage House, built as a garage for Ellen Browning Scripps' chauffeur's Ford automobile, has been retrofitted for archival storage, housing historic photographs, public records, private documents, and newspaper archives. In 2018, the society acquired the Venturi Pergola, one of the postmodern structures designed by Venturi, Scott Brown and Associates for the Museum of Contemporary Art San Diego. Its Tuscan-inspired fiberglass columns and aluminum frame were a response to Irving Gill's early twentieth-century work, connecting the campus's architectural timeline across more than a hundred years.

Today the La Jolla Historical Society operates as a unique historic house museum that crosses disciplinary boundaries. Programs include exhibitions, architecture tours, youth education, and annual events like the Secret Garden Tour of La Jolla and the La Jolla Concours d'Elegance. The society consults with the City of San Diego on landmark designations for La Jolla properties. In 2014, the Historical Resources Board recognized the organization with an award for the Architectural Rehabilitation of Wisteria Cottage, and Save Our Heritage Organisation named the society Preservationists of the Year. The Randolph Collection, now nearly ninety years old, continues to grow. Each building on the campus represents a choice to save rather than demolish, to remember rather than forget. In a community that has reinvented itself repeatedly, from fishing village to artists' colony to research hub, the La Jolla Historical Society holds the thread connecting all those identities.