After serving as a Methodist pastor from 1916 to 1919 in Sanborn, New York, Pfeiffer taught at Harvard University beginning in 1922.
He was named to the Hancock Professor of Hebrew and Other Oriental languages in 1953, announced by the provost Paul H. Buck.
He was buried at Mount Auburn Cemetery in Cambridge, Middlesex County, Massachusetts.
Pfeiffer's works include The Archives of Shilwateshub (1932); Excavations at Nuzi, volumes 2 (1933) and 4 (with E.R.
Pfeiffer wrote a number of papers on philological, literary, and historical-critical criticism of the Bible.