The history of the Claude Moore Health Sciences Library is directly linked to Thomas Jefferson, founder of the University 1819. Mr. Jefferson personally selected the books for the University's Library. He commissioned a Boston bookseller in 1825 to purchase $15,000 worth of books from Europe, numbering about 8,000 volumes, housed in the Rotunda. His collection choices included 710 volumes in the medical sciences to support the Department of Anatomy and Medicine under Dr. Robley Dunglison.

The Library struggled through its early years, with meager funding. The time of the Civil War was particularly difficult. Funds finally became available in 1880 to acquire a subscription to Index Medicus, which had just been published by the precursor to the National Library of Medicine. In the eighteen-nineties, the first card catalog was completed. The medical faculty made an attempt to separate the Medical Collection from the General Library Collection and place it in the Anatomical Theatre. Had they been successful, the medical books would have been spared the terrible tragedy of the burning of the Rotunda in 1895. As it was, the entire Medical Collection, and most of the General Collection, was lost. The Library had to be totally rebuilt, mostly from generous gifts from alumni and other concerned individuals.

The beginning of the twentieth century saw professors at the University resorting to their own personal funds in order to provide materials for teaching. The hardship was most severe in the Medical Department due to the unusually large number of journals in the medical sciences and their high cost. In a step toward independence, a separate card catalog was created for the Medical Collection. In 1929, a new Medical School Building opened. This unified all the medical departments, which had been scattered throughout the Grounds. The Medical Collection became the Medical Library, and moved into new quarters in the Medical School Building. Despite its physical separation, however, the Medical Library was still a part of the University Library. In the 1940s and 1950s, funds for books and journals were scarce, although control of the Medical Book Fund was finally transferred from the University Library to the Medical School Dean.

In September 1962, Dr. Wilhelm Moll arrived and assumed his duties as Director of the Medical Library. Most significantly, his position now reported directly to the Medical School Dean. (Today, the Library Director reports to the Executive Vice President for the Health System.) Dr. Moll began planning for a new building which would house not only the scattered medical collections, but would incorporate the separate Nursing Library as well. The $2.3 million project was funded with a $1.5 million grant from the federal government, more than $500,000 raised by University alumni, friends, foundations, and some State appropriations. In April 1976, the new library building was dedicated and named the Claude Moore Health Sciences Library for Dr. Moore's generous donation.

Following Dr. Moll's untimely death in 1979, Terry Thorkildson was Library Director until 1990. A key accomplishment during this time was the automation of the Library's card catalog.

Linda Watson, the Director from 1990-2005, transformed the Library into a modern research library. While at UVA, she oversaw a major expansion and renovation project and lead the library through the early years of the Internet. In 2005, Watson left UVA to assume the position of the Director of the University of Minnesota Health Sciences Library.

In August 2005, Gretchen Arnold was appointed Interim Director and then Director of the library in 2007. She oversaw a renovation project that increased the amount of study space and the size of the After Hours room. Her tenure focused on forging and developing strong collaborations in the Health System and across Grounds.  In 2020, Gretchen led the library through significant challenges created by the COVID-19 pandemic, which included moving to full remote with the rest of the University and then a return to onsite services.  Gretchen retired in the fall of 2020, having led the library through a highly unstable summer dominated by a global pandemic.  At the time of her retirement, the library was one of the first to return to onsite services and viewed as a key partner at UVA Health.  

In September 2020, Dr. Bart Ragon was appointed Interim Director and then Director of the library in 2022.  Bart's tenure has focused on evolution of library services throughout the pandemic and the integration of the library with the UVA Health strategic plan, One Future Together.