O’Brien has been at Marquette for more than 30 years joining the university in 1981 as the parking and traffic manager. She then held a variety of positions in the bursar's office until she became Marquette's bursar in 1995, where she was responsible for the general administration and management of the billing and collection activities for the university. O'Brien also served as assistant vice president of administration and assistant executive vice president prior to becoming associate senior vice president in 2002. She has chaired numerous search committees, including the renewal task force and great service to students.
She is a graduate of the University of Wisconsin Oshkosh. Her husband, Peter, is a graduate of Marquette University's class of 1979. Their daughter Amy is a senior in the College of Education, and their son Michael is a sophomore in the Diederich College of Communication.