Mary Lyon, the founder of Mount Holyoke Female Seminary, was Principal of the school from 1837 until her death in 1849. Her successors as Principal were Mary C. Whitman (1849-1850), Mary W. Chapin (1850-1865), Sophia D. Stoddard (Acting Principal, 1865-1867), and Helen M. French (1867-1872). In 1888, Elizabeth Blanchard, who had served as Principal since 1883, was named Acting President when Mount Holyoke's charter was changed to allow the school to grant degrees. Mary A. Brigham was elected President in 1889, but died in a railway accident on the way to assume her duties. Louise F. Cowles was Acting President until Elizabeth Storrs Mead became the first non-alumna President of the College in 1890. Her successor, Mary Emma Woolley, was elected President in 1900, took office in 1901, and served until 1937. In a controversial appointment, Roswell Gray Ham then became Mount Holyoke's first male President. His successor, Richard Glenn Gettell, was President until his resignation in 1968. Academic Dean and history professor Meribeth E. Cameron, who had served as Acting President when Presidents Ham and Gettell were on leave in 1954 and 1966, filled that office once again until David B. Truman became President in 1978. His successors as President have been Elizabeth T. Kennan (1978-1995) and Joanne V. Creighton (1996-present). History professor Joseph J. Ellis was Acting President for the spring semester in 1984 when President Kennan was on sabbatical, English professor Peter Berek served as Interim President from June-December 1995, and psychology and education professor Beverly D. Tatum was Acting President for the spring semester in 2002 when President Creighton was on sabbatical. Lynn Pasquerella, a 1980 graduate of Mount Holyoke, became President of the College on July 1, 2010.

Biographical files concerning the Principals and Presidents of Mount Holyoke College date from circa 1875 to the present and contain primary and secondary sources relating to these individuals. Materials concern those who have served as principals or presidents of Mount Holyoke as well as those who have been acting or interim principals and presidents. These materials consist of correspondence and writings by them, curriculum vitae and resumes, books, biographical sketches, press releases, genealogical information, obituaries, tributes, notes, audiocassettes, compact discs, and photographs. The files for Mary Emma Woolley include recollections about her by alumnae in the Classes of 1905-1938. Files for Elizabeth T. Kennan and Lynn Pasquerella contain Mount Holyoke College records from their years as students at Mount Holyoke. Materials relating to Joseph J. Ellis (Acting President, January-June 1984) contain six audiocassettes of an interview of him on C-SPAN's "Booknotes" program in 1997, seven compact discs containing fourteen lectures by him concerning the "Brotherhood of the Revolution: how America's founders forged a new nation," recorded for the Modern Scholar program in 2004, and eight compact discs containing his lectures about "Patriots: Brotherhood of the American Revolution," recorded for the Barnes and Noble "Portable Professor" Series, 2004. Materials for Joanne Creighton include a video recording of her introduction to the Mount Holyoke community as President-Elect in 1995. The files also include memorabilia that belonged to some of these individuals and information about their families.

Materials are arranged by the tenure in office of each individual.