Born in Bristol, Tennessee, Ford began his radio career as an announcer at station WOPI in Bristol, leaving in 1939 to study classical music and voice at the Cincinnati Conservatory of Music. 1st Lieut. Ford served in World War II as the bombardier on a B-29 Superfortress flying missions over Japan. After the war, Ford worked at radio stations in San Bernardino and Pasadena, Calif. before signing a recording contract with Capitol Records in 1949 when he became a local TV star over Cliffie Stone's popular Southern California "Hometown Jamboree" TV show. He released almost 50 country singles through the early 1950s, several of which made the charts. Many of his early records, including "The Shot Gun Boogie," "Blackberry Boogie," and so on were exciting, driving boogie-woogie records featuring exciting accompaniment by the Hometown Jamboree band which included Jimmy Bryant on lead guitar and pioneer pedal steel guitarist Speedy West. "I'll Never Be Free," a duet pairing Ford with Capitol Records pop singer Kay Starr, became a huge country and pop crossover hit in 1950.

Ford eventually moved on from Hometown Jamboree. He took over from bandleader Kay Kyser as host of the TV version of NBC quiz show "College of Musical Knowledge" when it returned briefly in 1954 after a four-year hiatus. He also portrayed the 'country bumpkin' "Cousin Ernie" on I Love Lucy.

Ford scored an unexpected hit on the pop charts in 1955 with his rendition of Merle Travis' "Sixteen Tons," a sparsely arranged coal-miner's lament that Travis wrote in 1946, based on his own family's experience in the mines of Muhlenberg County, Kentucky. Its fatalistic tone contrasted vividly with the sugary pop ballads and the Rock and roll just starting to dominate the charts at the time:

You load sixteen tons, what do you get? Another day older and deeper in debt. Saint Peter, don't you call me, 'cause I can't go; I owe my soul to the company store... With a unique clarinet-driven pop arrangement by Ford's Musical Director, Jack Fascinato, "Sixteen Tons" spent ten weeks at number one on the country charts and eight weeks at number one on the pop charts, and made Ford a crossover star. It became Ford's 'signature song.'

Ford subsequently helmed his own primetime variety program, "The Ford Show," which ran on NBC from 1956 to 1961. Ford's program was notable for the inclusion of a religious song at the end of every show; Ford insisted on this despite objections from network officials who feared it might provoke controversy. It quickly became the most popular segment of the show. He earned the nickname "The Ol' Pea-Picker" due to his catch-phrase, "Bless your pea-pickin' heart!"

In 1956 he released "Hymns," his first gospel album, which remained on Billboard's "Top Album" charts for a remarkable 277 consecutive weeks; his album "Great Gospel Songs" won a Grammy Award in 1964. After the NBC show ended, Ford moved his family to Northern California and from 1962-65, hosted a daytime talk show The Tennessee Ernie Ford Show from San Francisco, broadcast over the ABC TV network.

Over the years, Ford has been awarded three stars on the Hollywood Walk of Fame, for radio, records, and television. He was awarded the Presidential Medal of Freedom in 1984 and was inducted into the Country Music Hall of Fame in 1990.

Ford, who offstage contended with a serious alcohol problem that never affected his professional work, began to suffer from increasing liver problems. He fell ill in 1991 after leaving a state dinner at the White House hosted by President George H. W. Bush, and died in a Virginia hospital on October 17, exactly thirty-six years after "Sixteen Tons" was released and one day shy of the first anniversary of his induction into the Hall of Fame.

Ford was posthumously recognized for his gospel music contributions by adding him to the Gospel Music Association's Gospel Music Hall of Fame in 1994.