Lou Anna Simon has a long history at Michigan State University (MSU), spanning over four decades. She enrolled at MSU in 1970 as a graduate student. She then joined the faculty and became the assistant director of the Office of Institutional Research.

In 1993, Simon served as the provost and vice president for academic affairs. Simon became the interim president in 2003 while current president Peter McPherson was helping to rebuild Iraq's economy. In January 2005, she became the first female president in the university's history.

Simon earned her PhD in administration and higher education from MSU in 1974. In addition, Simon also holds a master's degree in student personnel and counseling (1970), and a Bachelor of Arts degree in mathematics (1969), both from Indiana State University.

Simon resigned from the presidency on January 24, 2018. William "Bill" Beekman, vice president and secretary of the Board of Trustees from 2008 to 2018, briefly served as acting president. Former Michigan governor John Engler was voted interim president on January 31, 2018. Simon remained a John A. Hannah Distinguished Professor following her resignation.