Thomas was born in Olivia, North Carolina. He worked as a farmer and in a sawmill through the 1940s before his interest turned to auto racing. He participated in NASCAR's inaugural Strictly Stock race in 1949 and made four starts in the series' first season, adding thirteen more the following year after the division was renamed the Grand National Series. He recorded his first career win at Martinsville Speedway in a privateer Plymouth.
Thomas entered the 1951 season in a Plymouth before switching to a Hudson Hornet at the suggestion of fellow driver Marshall Teague. The change transformed his season: Thomas won the Southern 500 and five additional races in two months, ultimately defeating Fonty Flock for the Grand National championship in a late-season charge. Working with crew chief Smokey Yunick, Thomas became the first owner-driver to win the NASCAR championship.
The 1952 season brought a fierce rematch with a Flock, this time Fonty's younger brother Tim. Both drivers won eight races each in their Hudsons, but Tim Flock edged Thomas for the title in the final standings.
Thomas returned in 1953 to deliver one of the most dominant championship campaigns in NASCAR history. He won a series-best twelve races and took the title decisively, becoming the first two-time champion. He repeated the feat of twelve wins in 1954, including a second Southern 500 victory at Darlington — making him the first driver to win twice at that circuit — but greater consistency from Lee Petty denied him a third championship.
After four years piloting Hudsons, Thomas switched to Chevrolets and Buicks in 1955. A heavy crash at Charlotte in a Buick forced him to miss three months, but he returned to win his third Southern 500 in a Motoramic Chevrolet and finished fifth in the championship. In 1956, he drove for multiple owners including Smokey Yunick and Carl Kiekhaefer's dominant Chrysler operation, winning three consecutive races for Kiekhaefer before a severe crash at a race in Shelby, North Carolina, effectively ended his active career. Although he attempted two starts in 1957 and one in 1962, those final three victories with Kiekhaefer proved to be the last of his career.
Thomas finished with 48 wins, a figure that ranks seventeenth on NASCAR's all-time list, accumulated in just 228 starts — a ratio unmatched by any driver with a comparable volume of races.
Thomas and the Hudson Hornet he drove to his first championship served as primary inspirations for the character Doc Hudson in Pixar's Cars film franchise. The design of the fictional "Fabulous Hudson Hornet" racing car and its livery drew directly from Thomas's machines. A historical mural commissioned in 2016 by the City of Sanford, North Carolina, commemorates Thomas and the Fabulous Hudson Hornet on the side of a building at 133 N. Steele Street.
Thomas died of a heart attack on August 9, 2000, in Sanford, North Carolina, at age 77. He was inducted into the International Motorsports Hall of Fame in 1994, named one of NASCAR's 50 Greatest Drivers in 1998, inducted into the NASCAR Hall of Fame on February 8, 2013, and inducted into the Motorsports Hall of Fame of America in 2017. His younger brother Donald Thomas also competed in the Grand National division, winning at Atlanta's Lakewood Speedway in 1952 to become the youngest race winner in series history at the time, a record that stood until Kyle Busch broke it in 2005.