Before joining the faculty of the University of Oregon in 1962, Mazo was a postdoctoral fellow at Institute voor Theoretische Physica, University of Amsterdam and a research associate at the University of Chicago (sponsored by the National Science Foundation). He also held an assistant professorship at the California Institute of Technology.
Mazo's research interests were "Exclusively theoretical", and have included "Brownian motion processes, Markov processes, Probabilities, Statistical mechanics, and Transport theory."
During Mazo's 33 year career at the University of Oregon, he served at various times as chair of the chemistry department, director of the Institute Theoretical Science, and as associate dean of the graduate school. He was also a program director of the National Science Foundation.