Early in Williston's career, from 1888 to 1889 he worked as the private secretary to Supreme Court Justice Horace Gray. In the summer of 1889, he helped to collate laws from various U.S states in order to help formulate the state constitutions of North Dakota and South Dakota.
From 1895 to 1938, Williston served as a law professor at Harvard Law School, and in 1910, he briefly served as acting dean.
He became a consultant for the Boston law firm Hale & Darr from 1938 to 1956, during which time he was engaged in some Supreme Court cases such as "Kneeland v. AT&T" and "Chase National Bank v. Sayles." Williston actually argued the case of "Boston & Maine Railroad v. Hooker" before the U.S. Supreme Court on December 10 and 11, 1913, where he represented the defense for Hooker and ultimately lost the case.
First published during the span of 1920 to 1922, Williston wrote 5 volumes of "The Law of Contracts" which were widely acclaimed as the foremost authority on the topic and was later enlarged in 1938.
In 1929, Williston was honored with the very first American Bar Association medal for "conspicuous service to American jurisprudence."