Sarah Lee Odend'hal was born in Norfolk on November 23, 1888. She attended Leache-Wood Seminary and Hemmingway High School, from which she graduated in 1907. For the next twelve years, she taught in the Norfolk public schools and in the summer months took courses at the University of Virginia. Although as a woman she was not permitted to matriculate at the university, her summer studies were the equivalent of an undergraduate degree in education and administration. In September 1917, she married Walter Colquitt Fain, and shortly thereafter became active in a variety of women's organizations supporting the American effort in World War I (1914–1918).

Such activity sparked her interest in public life, and when the Nineteenth Amendment became law in 1920, she joined the Norfolk branch of the League of Women Voters and soon became active in Democratic Party politics. In 1922, she signed on to the campaign to reelect Virginia's U.S. senator Claude A. Swanson and was so successful in convincing Norfolk's newly franchised female voters to support him that several of her friends convinced her to run for a seat in the House of Delegates. She campaigned effectively in the Democratic primary and, on November 6, 1923, was elected to one of Norfolk's four assembly seats.

Fain was treated as a novelty and a celebrity when she arrived in Richmond in January 1924, but if observers expected her to behave in unorthodox ways, they were disappointed. She did not espouse a feminist agenda, as some of her detractors had feared she might, but rather focused on maritime and education issues that were important to her constituents. Challenged for her spot on the Democratic ticket in 1925, she won reelection handily, and when she stood for a third term in 1927, she was unopposed. In her third term, Fain chaired the Committee on Schools and Colleges and helped secure passage of an important education reform bill.

Fain did not seek a fourth term in 1929, but a year later tried unsuccessfully for a seat in Congress. She moved to Washington, D.C., in 1931, and worked for several New Deal agencies. Fain helped to found the U.S. Information Service and served as its first director. After stints in other federal positions in North Carolina and Texas, she moved to San Marino, California, in 1938. Fain did not run for public office again, but she did return to Norfolk to campaign for businesswoman Meeta B. Meyers in 1951 when she ran unsuccessfully for Fain's former seat. Fain died in California on July 20, 1962. The city of Norfolk did not elect another woman to the General Assembly until Evelyn Hailey in 1973.