He spent the early years of his career as an instructor, professor, and director of the choir at Bethany Lutheran College in Mankato, Minnesota (1936–1940); the University of Minnesota in Minneapolis-St. Paul (1940–1941); and Concordia Collegiate Institute in Bronxville, New York. In 1948, Hoffmann helped found the LCMS Department of Public Relations in New York City and served as its director until 1963.
He served as president of the Lutheran Council in the U.S.A. (1970–1973). A recognized authority on Latin and Greek, Hoffmann was chairman of the translations committee of the American Bible Society, and in 1977 he was elected president of the United Bible Societies.