[3] Papazian was born Mary Ellen Arshagouni to a family of Armenian descent in Santa Monica, California on February 25, 1959.

She then served as dean of the College of Humanities and Social Sciences at Montclair State University in New Jersey from 2004 to 2007.

Papazian was provost and senior vice president for academic affairs at Lehman College, City University of New York from 2007 to 2011.

[12] On October 7, 2021, Papazian announced that she would resign as the president of San José State University at the end of the 2021 fall semester.

[14][15] Papazian's dissertation at UCLA was titled John Donne's "Devotions upon Emergent Occasions": A Puritan Reading.