He was born in Barnet, Vermont. He spent much of his childhood in Rhode Island, where he started his working career. Flanders worked in the machine tool industry for most of his life. In his early career he wrote a number of articles on machine tool technology which led to an editorship of Machine magazine between 1905 and 1910. In 1911 he married Helen Hartness, daughter of inventor and industrialist James Hartness, who headed the Jones and Lamson machine tool company in Springfield, Vermont. Flanders worked as an engineer under Hartness at Jones and Lamson, and became president of the company after Hartness retired. He and his brother Ernest were instrumental in developing thread grinding machines based on the advances in thread technology created by the Hartness optical comparator. Flanders was the president of the Federal Reserve Board in Boston, Massachusetts from 1944 to 1946. In 1946 Flanders and some of his friends formed a venture capital company to help small Boston enterprises. The economic development that followed led to the now well known Route 128 technology ring around Boston. Flanders was appointed to the United States Senate as a Republican on November 1, 1946 to complete the term of Senator Warren Austin, who was appointed Ambassador to the United Nations. He was elected to a full term that same year. Flanders led the charge to censureJoseph McCarthy, speaking out against McCarthy on the Senate floor. He chose not to seek re-election in 1958. He was the author of a number of books, including Senator from Vermont, his autobiography. His wife, Helen Hartness Flanders, became well known as a folk song collector who authored several books on New England ballads.
Flanders appeared at the church forum March 5, and Elizabeth French of Springfield, his secretary at the time, believes it was the crowd's criticism of McCarthy that led to the Vermont senator's decision that the hour was at hand for a public statement on the matter.
Flanders said he was subjected to "persistent" questioning by the press in Melbourne where "the same question appeared and reappeared at luncheons, dinners and informal meetings." The senator continued in his memoirs, "At last it became clear that the impression was gaining ground that an American brand of Naziism was in the process of formation.
Flanders said McCarthy's headline-grabbing ventures were diverting the nation's attention from Korea, Indochina, Italy, France and England--lands that were in need of this country's attention and help as they fought to maintain their governments in the face of communist challenges.