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, considered a liberal Republican, led the charge to censure Joseph 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.