Frizzell influenced a number of other country singers, including George Jones, Willie Nelson, Roy Orbison, The Everly Brothers, Keith Whitley, Merle Haggard, and John Fogerty. He was inducted into the Country Music Hall of Fame in 1982. After the death of Hank Williams in 1953, Frizzell released many songs that charted in the Top 10 of the Hot Country Songs charts. His success did not carry on into the 1960s, and after suffering from alcoholism, he died at age 47.
William Orville Frizzell was born the son of an oilman, the first of eight children, in Corsicana in Navarro County in Central Texas. During his childhood, his family moved to El Dorado in Union County in south Arkansas. As a child he was called "Sonny," but later took the name "Lefty." It was believed they called him "Lefty" because he had won a neighborhood fight, however it turned out that this tale was a part of a fake publicity stunt set up by his label. Frizzell's largest influences included the blue yodeler Jimmie Rodgers. He began listening to Rodgers' records as a boy. He began singing professionally before his teens, even earning a spot on the local radio-station KELD El Dorado. Frizzell's teens were spent singing in nightclubs and radio and talent shows throughout the south. During his tour of Arkansas, Texas, New Mexico, and Las Vegas, he began to draw a style of his own, shaped from artists like Rodgers, Ernest Tubb, and Ted Daffan.
In 1947, the 19-year old Frizzell was arrested for having sex with an underage fan. He had been married only a year, and filled with guilt, he wrote poems to his wife from his cell; one of them would become his first big record. After release in late 1949, he was led away from music, and back to the oil fields with his father. However, soon he was performing in nightclubs again. By 1950, he had landed a regular job at the Big Spring, Texas nightclub "Ace of Clubs" where he developed a dedicated fan following. During a show there, Jim Beck, owner of a local recording studio, was starting to take notice of Frizzell. Beck had deals with several major record producing labels and maintained connections with the many publishers. Impressed with Frizzell's performance, he invited him to make a free demo at the studio. In April 1950, he cut several demos of Frizzell singing his own songs, including "If You've Got the Money (I've Got the Time)," which Beck took to Nashville where he pitched it to Little Jimmy Dickens, who disliked the song. However, Columbia Records producer Don Law heard the cut and liked it. After hearing Lefty in concert, he signed the singer and recorded him for the first time.
In 1954, Frizzell had an automobile accident near E.S. Richardson Elementary School in Minden in Webster Parish, Louisiana, through which he passed after leaving the Louisiana Hayride in Shreveport en route to a concert in Mississippi. His Cadillac struck the Nash station wagon parked at the home of its owner, R. Harmon Drew, Sr., the former city judge and later a member of the Louisiana House of Representatives. Frizzell apologized, said that he hoped to visit Minden again under more favorable circumstances, posted bond, and took a taxicab back to Shreveport, from which he flew to his destination.
Frizzell's signature guitar was a 1949 Gibson J-200 (Model SJ-200). Originally built by the Gibson Guitar Corporation, it was retrofitted in early 1951 with a custom neck and pickguard by guitar maker and innovator Paul Bigsby. In a 2003 interview Merle Haggard recalled, "When I was a teenager, Lefty got me onstage and handed me that guitar. That is the first guitar I played on a professional stage." For many years it had been on loan to and displayed at the Country Music Hall of Fame in Nashville, Tennessee. In January 2005 it was returned to the Frizzell family. It was later sold at auction by Retrofret,  with an asking price of $350,000. Merle Haggard purchased the guitar and it remains a part of his estate. 
"If You've Got the Money (I've Got the Time)" became a two-sided smash hit in 1950 upon its release. The b-side being the song Frizzell wrote to his grief-stricken wife from jail, "I Love You A Thousand Ways." The songs launched him into stardom and within two years, he had gone to register 13 Top 10 Country hits. By 1951, he had perfected his vocal style and refined his guitar skills. He began working with a core group of Dallas-based studio musicians, including pianist Madge Suttee. In the beginning of 1951, he formed the Western Cherokees, led by Blackie Crawford, and soon they became his primary band for both live and recording sessions. During his early career, Lefty was in the studio extensively, recording singles. His third "I Want to Be With You Always" was #1 for 11 weeks.
By mid-1951, Frizzell had become one of the only people that could be considered to match the popularity of Hank Williams; he had even toured with Williams. "There is enough stories in that tour to fill a book..." Frizzell once said, although he never told those stories. He had three more Top 10 hits in 1951; "Mom and Dad's Waltz, "Travelin' Blues," and the #1 hit "Give Me More, More, More (Of Your Kisses)." By 1952, he was a very popular stage performer and in heavy demand, being included on The Grand Ole Opry and The Louisiana Hayride multiple times throughout the 1950s. The hits continued throughout 1952, with "How Long Will It Take (To Stop Loving You)," "Don't Stay Away ('Till Love Grows Cold)", "Forever (And Always)", and "I'm An Old, Old Man (Try'n'a Live While I Can)".