Byron was born in Washington County, Virginia, and later moved to Colorado before settling in Anniston, Alabama, which he considered home. He began racing in 1932 and established a strong regional reputation at Talladega and Anniston before connecting with Raymond Parks — a former bootlegger turned vending machine operator — and crew chief Red Vogt at Lakewood Speedway in Atlanta.
In spring 1941, Byron enlisted in the United States Army Air Corps. He flew as a flight engineer and tail gunner on B-24 Liberator bombers, completing 58 missions. On his 58th mission, targeting Imperial Japanese forces at Paramushir, a hung bomb had to be manually freed from the aircraft floor. As Byron worked at the open bomb bay doors, an explosion tore his left leg to pieces. He spent 27 months in rehabilitation at Fitzsimons Army Medical Center. During recovery, Byron sketched devices to help him return to racing despite severely limited left-leg mobility. Working with Red Vogt in 1946, he fabricated stirrup pins on his clutch pedal that, combined with a leg brace, allowed him to operate the car.
Byron returned to competition in 1945 and won the Hankinson Memorial on February 24, 1946, at Seminole Speedway, beating Roy Hall and Bill France. He entered the 1941 Stock Car AAA series before the war interrupted his career.
When NASCAR formed in 1948, Byron joined Raymond Parks's team in the new Modified Series. He won the Rayson Memorial — the first NASCAR-sanctioned race — at the Daytona Beach Road Course, beating Marshall Teague and Bob Flock. The season unfolded as an intense points battle with Fonty Flock. Byron accumulated 11 wins and 25 top-five finishes across the season. Despite a tragic accident at Columbus Speedway in July — a blown tire sent his car into spectators, killing a seven-year-old boy and injuring sixteen others, though Byron was unhurt — he battled back through the second half and clinched the title at the season finale at Columbus Raceway in November.
In 1949, NASCAR launched a new Strictly Stock series for contemporary production cars. Byron ran the full eight-race inaugural season with Parks. He won at the Daytona Beach Road Course and at Martinsville Speedway, where he led 97 of the race's laps. Those two victories, combined with consistent finishes, gave him the championship by 117.5 points over Lee Petty. Byron was NASCAR's first Strictly Stock champion, and the series itself would become the sport's crown jewel.
Byron raced only four times in the 1950 Grand National season and five times in 1951 as his war injuries continued to deteriorate his health. His final NASCAR start came at the 1951 Southern 500 at Darlington Raceway, where he finished 25th after an accident. After retiring from driving he remained active in motorsport, working with Briggs Cunningham on efforts to develop an American sports car capable of winning major European races, and later managing a Corvette team. At the time of his death on November 11, 1960 — a heart attack in a Chicago hotel room — Byron was managing the Scarab SCCA team and was scheduled to fly to Daytona the following day for a championship race.
Byron was named one of NASCAR's 50 Greatest Drivers in 1998 for the sport's 50th anniversary, and was automatically included on the 75 Greatest Drivers list in 2023. He was inducted into the National Motorsports Hall of Fame in 1966, the International Motorsports Hall of Fame in 2008, the NASCAR Hall of Fame on January 19, 2018, and the Motorsports Hall of Fame of America in 2020. His achievement of winning the very first championships in two different NASCAR divisions in consecutive years, as a competitor operating a specially modified clutch to compensate for a combat injury, places him among the most remarkable figures in the sport's founding era.