Phillips started his academic career as an assistant professor at the University of Illinois Urbana-Champaign, followed by his appointment as a professor of biochemistry at Rice University in 1987. In 1993, he assumed the position of Rice Scientia Lecturer, subsequently receiving the Robert A. Welch Lecturer appointment in 2001. He joined the University of Wisconsin-Madison in 2000 as a professor of Biochemistry and took on the role of professor emeritus in 2012. He has been serving as a professor of chemistry, as well as the Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology at Rice University.