Trefonas joined MEMC Electronic Materials in late 1984.  In 1986, he and others co-founded Aspect Systems Inc., utilizing photolithography technology acquired from MEMC.  Trefonas worked at Aspect from 1986-1989. Then, through a succession of company acquisitions, he moved to Shipley Company (1990-2000), Rohm and Haas (1997-2008), to The Dow Chemical Company (2008-2019), and finally to DuPont (2019-current).
Trefonas has published at least 132 journal articles and technical publications. He has received 107 American patents, and has more than 15 active patent applications pending.