Prendergast taught Latin and Greek at Loyola High School in Montreal from 1967 to 1969. After he became a priest and earned his Doctor of Theology degree, he taught in Halifax at the Atlantic School of Theology from 1975 to 1981. He was the rector of Toronto's Regis College from 1981 to 1987, and its Dean of Theology from 1991 to 1994. From 1992 to 1994 he helped Bishop Frederick Henry visit English-language Canadian seminaries for the Vatican. When he was asked to be Auxiliary Bishop of Toronto in 1995, he was a Visiting Professor at the École Biblique in Jerusalem.