Mayfield graduated from Southwestern University in 1900 and subsequently studied law at the University of Texas at Austin. He was admitted to the bar in 1907 and practiced in Meridian, Texas for some time; in addition, he pursued business ventures in agriculture and the wholesale grocery industry. Between 1907 and 1913, he held a seat in the Texas State Senate, after which he served on the State Railroad Commission for ten years.

In 1922, Mayfield was one of six candidates who challenged five-term United States Senator Charles A. Culberson for the Democratic nomination for the Senate. In the ensuing primary runoff between Mayfield and former Texas governor James Ferguson, Mayfield was labelled the "Klu Klux Klan candidate" due in part to both he and the klans support of prohibition, while Ferfuson's anti-prohibition stance was emphasized. After securing the endorsement of longterm Texas Senator Morris Sheppard, Mayfield won the Democratic nomination. In the general election Mayfield faced independent candidate George Peddy, who challenged the election results, alleging a range of technical missteps. A Senate committee finally ruled in favor of Mayfield after a two-year investivation.

Mayfield once again faced a large field of candidates in the Democratic primary in 1928, but this time was defeated by Congressman Tom Connally. In 1930 he tried for the Democratic nomination for governor, but only finished seventh out of eleven candidates. After losing his Senate seat, he moved to Tyler, where he retired in 1952.

This article incorporates facts obtained from the public domain Biographical Directory of the United States Congress.