Scott was born in Danville, Virginia, a city dominated by cotton mills and tobacco-processing plants. His father worked as a driver and mechanic for two white families, and Scott learned auto mechanics from him from an early age. He dropped out of high school, worked as a taxi driver, and served as a mechanic in the segregated United States Army during World War II. He married Mary Coles in 1943 and they had seven children.
After the war Scott ran an auto-repair shop and, as a secondary income, operated as a moonshine runner. He was caught once, in 1949, and sentenced to three years of probation.
In 1951 officials at the Dixie Circuit, a regional racing organization, recruited Scott as a marketing exercise. He won his first race at Lynchburg, Virginia, only twelve days into his racing career and quickly became a competitive regular on Virginia tracks, at times running five events a week. Fellow drivers would sometimes serve as informal bodyguards at venues with hostile crowds, though some prejudiced competitors deliberately wrecked him.
Scott won dozens of regional races over nine years, including two championships in 1959: the NASCAR-awarded Virginia sportsman-class championship and the track championship at Richmond's Southside Speedway.
In 1954, Scott towed his car to Richmond Speedway and persuaded local steward Mike Poston to issue him a NASCAR license, becoming the first Black driver to hold one. He stepped up to the Grand National Series on March 4, 1961, in Spartanburg, South Carolina, achieving the most points for a debutant that season.
His signature result came on December 1, 1963, at Speedway Park in Jacksonville, Florida, a half-mile dirt track. Driving a Chevrolet Bel Air purchased from Ned Jarrett, Scott passed Richard Petty with 25 laps remaining and won the race — the first Grand National victory by an African-American driver. Race officials initially declared Buck Baker the winner; they corrected the result two hours later when it became apparent Scott had not only won but lapped most of the field. Despite the official correction, his family did not receive the trophy he had earned until 2021, nearly 58 years after the race and 31 years after Scott's death.
Despite receiving no commercial sponsorship throughout his career, Scott posted competitive finishes against far better-funded teams. He finished 6th in points in 1966, his career high, and ranked in the top ten in points in 1966, 1967, 1968, and 1969. His best year financially was 1969, when he won $47,451 in prize money.
Scott's career ended as a consequence of injuries sustained in a racing accident at Talladega in 1973, though he made one further start at the 1973 National 500, finishing 12th.
Scott's wife Mary drove the truck that transported his race car to events, and the family traveled together. His daughter Sybil later became a consultant for NASCAR's Drive for Diversity program, which works to increase the participation of women and minorities in the sport. His son Wendell Jr. died in 2022.
Scott died on December 23, 1990, in Danville, Virginia, from spinal cancer.
Scott was posthumously inducted into the International Motorsports Hall of Fame and the NASCAR Hall of Fame in 2015. He received a historical marker in Danville in January 2013. The 1977 film Greased Lightning, starring Richard Pryor, was based loosely on his story. A fictionalized version of Scott appeared in the 2017 Pixar film Cars 3, portrayed by Isiah Whitlock Jr. under the name River Scott.
Only a small number of other African-American drivers are known to have started at least one race in what is now the NASCAR Cup Series. Scott's career, conducted against systemic opposition and with minimal resources, established the precedent for all of them.