Kefauver was born in Madisonville, Tennessee, to Robert Cooke Kefauver and Phredonia Bradford (Estes). Robert Kefauver was a hardware manager. Estes attended the University of Tennessee from 1922 to 1924, receiving a bachelor of arts degree and being initiated into the Lambda Chapter of the Kappa Sigma Fraternity. After a year of teaching mathematics and coaching football at a Hot Springs, Arkansas, high school, he attended Yale Law School, from which he received an LL.B. cum laude in 1927. For the next dozen years Kefauver practiced law in Chattanooga, first with the firm of Cooke, Swaney & Cooke, as a partner in Sizer, Chambliss & Kefauver, and later in the firm of Duggan, McDonald, & Kefauver. In 1935 he married Nancy Pigott of Glasgow, Scotland, eight years his junior, whom he had met during her visit to relatives in Chattanooga. They raised four children, one of them adopted. Mrs. Kefauver died in 1967.
Aroused by his role as attorney for the Chattanooga News, Kefauver became interested in local politics and sought election to the Tennessee Senate in 1938. He lost but in 1939 spent two months as Finance and Taxation Commissioner under the newly-elected governor Prentice Cooper. When Congressman Sam D. McReynolds of Tennessee's 3rd district, which included Chattanooga, died in 1939, Kefauver was elected to succeed him in the House.
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