Wilson spent the early years of her career as an assistant professor of philosophy at Columbia University (1965–1967), and went on to teach at the Rockefeller Institute between 1967 and 1970.

During her tenure at Princeton she shared a department with other prominent philosophers including David Lewis, Saul Kripke, Harry Frankfurt, Gil Harman, Bas van Fraassen, Paul Benacerraf and Richard Jeffrey.

[4] Wilson taught courses in Descartes, Spinoza and Leibniz, Locke, Berkeley and other early modern philosophers as well as the Philosophy of Religion.

[8] Margaret Wilson has been described as "the most eminent English-language historian of early modern philosophy of her generation"[9] was awarded many honors over the course of her distinguished career, and was among only a handful of prominent female philosophers in a field overwhelmingly dominated by men.

Active in professional organizations, Wilson served as vice-president of the Eastern Division of the American Philosophical Association (APA) for 1993-94 and for 1994–95.