Born and raised in New York, she worked for Sol Lewitt while in art school and began exhibiting her work at the age of twenty. Interested in the conceptual aspect of artmaking, Piper experimented with politically charged performances that confronted sensitive subject matter. Many of Piper’s works, ranging from video to performance to installation, entangle her viewers in the moral, social, and political complexities of racial identity. Throughout her practice, her sharp commentary challenges the neutrality of the "subject" that is often assumed in art and mass media, and addresses gender, race, xenophobia, social engagement, and selfhood.

In addition to her career in the arts, Piper has been deeply involved in philosophical studies, and taught philosophy at Harvard University, University of Michigan, and Stanford University. Her writings have primarily focused on metaethics, Kant, and the history of ethics. In 2008, she published Rationality and the Structure of the Self. Volume I: The Humean Conception, a two-volume study on Kantian metaethics. While teaching at Georgetown in 1987, she became the first tenured African American woman professor in the field of philosophy.

Piper received an AA from the School of Visual Arts, a BA from City College of New York, and a PhD in philosophy from Harvard University. Her numerous awards include fellowships from the Guggenheim and the National Endowment for the Arts, as well as the Golden Lion Award for Best Artist at the 2015 Venice Biennale. The Studio Museum has presented her work in exhibitions including Tradition and Conflict (1985); Art as a Verb: The Evolving Continuum: Installations, Performance, and Videos by 13 African-American Artists (1989); and Photography Past/Forward: Aperture at 50 (2002).