In 1958, Roger Revelle's efforts to establish an Institute of Science and Engineering adjacent to the Scripps Institution of Oceanography were spearheaded by his desire to immediately construct a science and library building on the present Revelle College site. When the university was eventually constructed, university librarian Melvin Voigt devised a plan to purchase books for the three new UC campuses: UC San Diego, UC Santa Cruz, and UC Irvine. The first Science and Engineering Library in Urey Hall satisfied the science-focused school's needs.

However, as faculty recruits began to found social science and humanities departments, it became clear to Chancellor John Semple Galbraith that the time had come to establish the campus's main library collections. One of the conditions of Galbraith's acceptance of the UC San Diego chancellorship had been that UC San Diego would house one of the three great libraries of the UC system.[1] To accomplish this end, he formed a committee which commissioned architect William L. Pereira to prepare a master plan for the University Center and its focal point, the Central Library.[2] Pereira and his team, who were still retained as campus architects by UC Irvine, produced the plans and designs from their Urbanus Square facility in Irvine.

Pereira's plan called for the University Center to be moved north and east, along with the proposed library building. This resulted in a revision of the campus long-range development plan: the three "clusters" of four colleges each would be more compact, allowing for an auxiliary library in each cluster. The proposed building was designed around a spheroidal tower, to maximize the stacks area that could be accessed in a given time from the center. This tower was to be situated atop a main level containing the staff and public areas of the library.

The chosen site allowed for future expansions to step downwards into the canyon. Construction of the first of three increments began in July 1968; the two main floors were constructed first to form the base of the structure. This allowed for the placement of scaffolding to support construction of the tower. The Central University Library building's topping-out ceremony took place in December 1969 and its formal dedication was in March 1971.[2]

Central Library, combined with the original Scripps Library, the Humanities-Library building (now Galbraith Hall) in Revelle College, and the Biomedical Library (built in 1969),[3] was able to support and represent the growing university for years. In 1990, construction began on a two-story, 136,850 square foot subterranean expansion of the main level. The project included renovation of the existing facility to comply with safety standards and cost $38 million, provided by California's 1988 Proposition 78.[4] The expansion, designed by Gunnar Birkerts, was completed in February 1993.[5] In 1995, La Jolla resident Audrey Geisel donated $20 million to the UC San Diego Library, supplementing her 1991 donation of $2.3 million worth of her husband Theodor Seuss Geisel's original works. In exchange, the library was renamed Geisel Library.[6]

Between the first and second renovations of Geisel Library, several other UC San Diego library facilities were also renovated or closed. The biomedical library received a $17 million, 43,454 square foot expansion in 2006.[7] In 2011, the SIO library, the IR/PS library, the Hillcrest Medical Center library, and the Center for Library Instruction and Computing Services (CLICS) were closed and their collections consolidated into Geisel Library due systemwide budget cuts.[8] In 2015, university officials announced that Geisel Library would begin to undergo its second renovation. This renovation includes construction of a café named Audrey's on the main level of the library.[9]

Geisel Library's current name has come under increasing criticism over the last few years due to increasing awareness of Theodor Geisel's own expression of anti-Blackness, Orientalism, and other racially-charged beliefs[10] through cartoons and other work that he produced throughout the majority of his career. Although Theodor Geisel did come to renounce his more racially offensive characterizations during an interview for his alma mater of Dartmouth College, there has been no official response by UC San Diego to students requesting a name change.[11]