He has been a voice in debates on animal studies and advocates a version of the posthumanist position.
In 1984 Wolfe read interdisciplinary studies in English, philosophy, and comparative literature at University of North Carolina at Chapel Hill, where he received a B.A.
Wolfe's first teaching position was as an assistant professor at Indiana University, Bloomington, in 1990.
At Albany, he later served as director of graduate studies, associate chair, Department of English, 1998–1999, and was made a full professor in 1999.
In 2003, he was accepted an endowed professorship, the Bruce and Elizabeth Dunlevie post, at Rice University.