Although born in Indiana, the future U.S. Secretary of State grew up in Warsaw, Illinois. He attended Brown University in Rhode Island before becoming the secretary of fellow Illinoian, President Abraham Lincoln. In 1865 Hay became secretary to the U.S. legation at Paris, going next to Vienna and traveling to Turkey, Poland, and Spain. Upon his return to the United States, he became a journalist, working under Whitelaw Reid. In 1878 he became assistant secretary of state and became part of a Washington group that included Henry Adams, Henry Cabot Lodge, and others. During the 1880s and 1890s, he became a major author and, with John Nicolay, wrote an influential biography of Lincoln.

When his friend William McKinley became President, Hay was named ambassador to Great Britain in 1897. Some of the recognition of the longstanding community of interests between that country and the United came as a result of Hay's stay there. Conversely, he frequently informed McKinley of European attitudes toward U.S. initiatives.

In August 1898, Hay was named Secretary of State and helped negotiate the Treaty of Paris. His contributions included the adoption of an open door policy in China and the preparations for the Panama Canal. He is also renowned for his comment, written in a letter to President Theodore Roosevelt, describing the Spanish American War as a "splendid little war."