From its founding in 1887 until 2023, the Newberry Library has had ten Librarians and one Interim Librarian. They are: William F. Poole (1887-1894), John Vance Cheney (1894-1909), W. N. C. Carlton (1909-1920), George B. Utley (1920-1942), Stanley Pargellis (1942-1962), Lawrence W. Towner (1962-1986), Charles T. Cullen (1986-2005), David Spadafora (2005-2019), Daniel Greene (2019-2023), Gail Kern Paster (serving as Interim President and Librarian from April-October 2023), and Astrida Orle Tantillo (December 2023-current).

Appointed in 1887 by Newberry estate Trustees Blatchford and Bradley to organize the new library, William F. Poole worked under close Trustee supervision. Until 1914, when Trustee President E. W. Blatchford died, most aspects of library administration were controlled by the Trustees, a practice that diminished steadily, first in personnel matters and library organization, and later in book selection, under librarians Carlton, Utley, and Pargellis. The transfer of administrative responsibility to the Librarian was formalized in Bylaws revisions during the Towner years and is reflected in job title changes: Director and Librarian, 1965-1974, President and Librarian, 1975-present.