Educated at Randolph-Macon College and Georgetown University Law School, Prettyman began the practice of law in Hopewell, Virginia in 1915. After serving in the United States Army during World War I, he spent the next three and one-half decades either in private practice, working as a corporation counsel, or working for the U.S. Bureau of Internal Revenue. In 1945, President Harry S. Truman appointed Prettyman to the bench to fill the seat vacated by Judge Justin Miller. From 1958-1960, he served as Chief Judge of the court.
In 1997, the E. Barrett Prettyman Federal Courthouse was named in his memory. Years earlier, Prettyman had advocated the establishment of the triangular 24-foot high monument with excerpts and scenes from the nation’s founding documents that sits in front of the Courthouse.