On the Taft Court, Stone joined with Justices Oliver Wendell Holmes Jr. and Louis Brandeis in calling for judicial restraint and deference to the legislative will.

On the Hughes Court, Stone and Justices Brandeis and Benjamin N. Cardozo formed a liberal bloc called the Three Musketeers that generally voted to uphold the constitutionality of the New Deal.

Stone was the chief justice in Korematsu v. United States (1944), ruling the exclusion of Japanese Americans into internment camps as constitutional.

His father wished him to become a scientific farmer, and Stone matriculated at the Massachusetts Agricultural College where he attended classes[5] from 1888 to 1890[5] and was later expelled at the end of his second year for a scuffle with an instructor.

During World War I, Stone served for several months on a War Department Board of Inquiry, with Major Walter Kellogg of the U.S. Army Judge Advocate Corps and Judge Julian Mack, that reviewed the cases of 2,294 men whose requests for conscientious objector status had been denied by their draft boards.

"[10] At the end of the war, he criticized Attorney General A. Mitchell Palmer for his attempts to deport aliens based on administrative action without allowing for any judicial review of their cases.

"[13] In 1923, disgusted by his conflict with Butler and bored with "all the petty details of law school administration" that he dubbed "administrivia", Stone resigned the deanship and joined the prestigious Wall Street firm of Sullivan & Cromwell.

[14] He received a much higher salary and headed the firm's litigation department, which had a large corporation and estate practice (including J.P. Morgan Jr.'s interests).

[12] In full‑time private practice for only a brief time, Stone was considered a "hard‑working, solid sort of person, willing on occasion to champion the rights of mankind, but safe nevertheless.

"[15] On April 1, 1924, he was appointed United States Attorney General by his Amherst classmate President Calvin Coolidge, who felt Stone would be perceived by the public as beyond reproach to oversee investigations into various scandals arising under the Harding administration.

A pro‑active Attorney General, Stone argued many of his department's cases in the federal courts and launched an anti‑trust investigation of the Aluminum Company of America, controlled by the family of fellow cabinet member Andrew Mellon, Coolidge's Secretary of the Treasury.

[12] He especially opposed the left-wing Progressive Party's candidate, Robert M. La Follette, who had proposed that Congress be empowered to reenact any legislation that had been struck down by the Supreme Court.

[12] The Court utilized the doctrines of substantive due process and the fundamental right of "liberty of contract" to oversee attempts at regulation by the national and state governments.

Critics of the Court charged that the judiciary had usurped legislative authority and had embodied a particular economic theory, laissez faire, into its decisions.

For example, he wrote for the court in United States v. Darby Lumber Co.,[19] 312 U.S. 100 (1941), which upheld challenged provisions of the Fair Labor Standards Act of 1938.

Stone also authored the Court's opinion in United States v. Carolene Products Co.,[20] 304 U.S. 144 (1938), which, in its famous "Footnote 4", may have provided a roadmap for tiered scrutiny in the post-Lochner v. New York era.

[8] As chief justice, Stone spoke for the Court in upholding the President's power to try Nazi saboteurs captured on American soil by military tribunals in Ex parte Quirin,[22] 317 U.S. 1 (1942).

[23] Stone also wrote one of the major opinions in establishing the standard for state courts to have personal jurisdiction over litigants in International Shoe Co. v. Washington,[24] 326 U.S. 310 (1945).

[32][33] Columbia Law School awards Harlan Fiske Stone Scholarships to students who demonstrate superior academic performance.

[34] Yale Law School awards the Harlan Fiske Stone Prize each fall to winners of the Morris Tyler Moot Court competition.