The Institute for American Thought, housed in the School of Liberal Arts, supported interdisciplinary faculty research, and sponsored conferences and special events at the university. The institute was first established as the Center for American Studies in 1975 as a research component of the IUPUI School of Liberal Arts. Bernard Friedman served as the institute's first director and was designed as an interdisciplinary program with an emphasis on history, literature, religion, and philosophy. In 1976, the Charles Sanders Peirce Editorial Project was brought to IUPUI and housed within the Center for American Studies as their first major project. In 1981, the center launched two new scholary publications: the Journey of the Early Republic and the Journal for Teaching Writing. The Center later changed its name to the Institute for American Thought.

The institute served as an incubator for several projects and iniatitves that grew into other academic units including the Center for the Study of Religion and American Culture, the POLIS Center, and the School for Philanthropy. Editorial work on the Journal of the Early American Republic and Journal for Teaching Writing was done in association with the Center, and the Charles S. Pierce Project, Frederick Douglass Papers, and the George Santayana Edition projects were associated with the institute. The institute was instrumental in developing the American Studies program at IUPUI with the creation of courses, majors, and minors. In 2015, the School of Liberal Arts created the first doctoral program in American Studies. THe program welcomed its first doctoral students in 2017.