Hamilton Fish entered public life after legal practice in New York. A Whig, he served in the House of Representatives, became lieutenant governor and then governor of New York, and sat in the United States Senate from 1851 to 1857. As the Whig Party disintegrated he joined the Republicans. During the Civil War he assisted Union support work in New York and participated in efforts concerning prisoners and exchanges.

President Ulysses S. Grant appointed him secretary of state in 1869. Fish brought experience and a preference for negotiation to an administration facing disputes left by the Civil War. Claims against Britain for damage caused by Confederate cruisers, including the Alabama, were especially contentious. He helped develop the negotiations that produced the Treaty of Washington in 1871 and referred the Alabama claims to international arbitration.

The Geneva tribunal's award in 1872 required Britain to pay the United States $15.5 million. The settlement became an important example of arbitration between major powers. Fish's work involved managing relations with the Senate and British representatives as well as shaping the terms of agreement; it was a diplomatic process involving several negotiators and commissioners.

Cuba presented another recurring problem. Fish resisted recognizing rebels fighting Spanish rule as belligerents, seeking to protect American interests without provoking war with Spain. In the Virginius crisis of 1873, after Spanish authorities captured a vessel and executed passengers and crew, he negotiated for the return of the ship and survivors and further consideration of claims. He also dealt with unsuccessful territorial ambitions and disputes along the Mexican border. Remaining in office until 1877, he provided continuity through Grant's presidency. His career is especially associated with using diplomacy and legal procedures to contain conflicts that stirred public emotion, within the limits imposed by domestic and foreign politics.