Wills was born in Seagoville in Dallas County, Texas. He was a performer from early childhood, forming and leading the Avalon Boys singing group in the 1930s. After appearing with them in a few westerns, he disbanded the group in 1938 and struck out on a solo acting career.
One of his more memorable roles was that of the distinctive voice of Francis the Mule in a series of popular films. Wills' deep, rough voice and Western twang were perfectly matched to the personality of the cynical, sardonic mule. As was customary at the time, Wills was given no billing for his vocal work, though he was featured prominently on-screen as blustery General Ben Kaye in the fourth entry, Francis Joins the WACS.
Wills also appeared in numerous serious roles, including that of Uncle Bawley in Giant, a 1956 film starring Rock Hudson, Elizabeth Taylor, and James Dean. Wills was nominated for Best Supporting Actor in 1960 for his role as Davy Crockett's companion "Beekeeper" in the film The Alamo. However, his aggressive campaign for the award was considered tasteless by many, including the film's producer, John Wayne, who publicly apologized for Wills. Wills' publicity agent, W.S. "Bow-Wow" Wojciechowicz, accepted blame for the ill-advised effort, claiming that his employer had known nothing about it. Wills was defeated for the Oscar by Peter Ustinov, who won for his role in Spartacus.
In 1966, Wills was cast in the role of a shady Texas rancher, Jim Ed Love, in the short-lived ABC comedy/western series The Rounders, with co-stars Ron Hayes (1929-2005), Patrick Wayne (born 1939), and Walker Edmiston (1926-2007).
Wills served as master of ceremonies for George C. Wallace, Jr., former governor of Alabama, for the California campaign stops in Wallace's 1968 Presidential campaign. He and Walter Brennan of The Real McCoys, The Tycoon, and The Guns of Will Sonnett, were among the few Hollywood celebrities to endorse Wallace's campaign against Hubert H. Humphrey and Richard M. Nixon.
Wills' last role was in 1978 as a janitor in Stubby Pringle's Christmas.