Scott was born in Danville, Virginia, a town centered on cotton mills and tobacco processing. He resolved as a youth to avoid factory labor, learning auto mechanics from his father and racing bicycles against neighborhood children. After dropping out of high school, he worked as a taxi driver and served as a mechanic in the segregated U.S. Army during World War II, gaining technical skills that would later sustain his career as a self-funded racing team.
After the war, Scott ran an auto-repair shop in Danville. As a sideline, he ran moonshine whiskey, a pursuit common in the region. Caught once in 1949, he received three years of probation. It was through the moonshine circuit that his driving reputation grew.
Scott began competing in 1951, recruited initially as a marketing novelty by the Dixie Circuit, a regional racing organization. He won his first race at Lynchburg, Virginia, only twelve days into his career. He raced across Virginia tracks, sometimes five events a week, developing a strong following even among white fans. Prejudiced drivers deliberately wrecked him at times; fellow competitors sometimes served as bodyguards at hostile events.
In 1954, Scott obtained his NASCAR license at the Richmond Speedway, becoming the first Black driver in NASCAR. He spent nine years in regional-level competition, winning dozens of races and two championships in 1959.
In 1961, Scott moved up to the Grand National Series. On December 1, 1963, driving a Chevrolet Bel Air purchased from Ned Jarrett, he won at Speedway Park in Jacksonville, Florida — becoming the first African-American to win at NASCAR's premier level. Scott passed Richard Petty with 25 laps remaining and finished two laps ahead of the field. Despite this, race officials initially declared second-place finisher Buck Baker the winner; NASCAR corrected the result two hours later, but Scott never received the physical trophy at the ceremony. His family did not receive the trophy he had earned until 2021, nearly 58 years after the race and 31 years after his death.
Scott's career was repeatedly disrupted by racial prejudice, including a poisoning incident at Dover and death threats at multiple tracks including Spartanburg, Darlington, Talladega, Jacksonville, and Daytona. He never received commercial sponsorship throughout his career, funding his own operation against factory-backed and well-financed teams.
Despite these obstacles, Scott was consistently competitive. He finished sixth in points in 1966, his career high, and placed in the top ten in points standings for five consecutive years from 1966 through 1969. His top earnings year was 1969, when he won $47,451. He achieved one Grand National win and 147 top-ten finishes across 495 career starts.
A racing accident at Talladega in 1973 forced Scott into retirement, though he made one additional start at the 1973 National 500 before concluding his career.
Scott died on December 23, 1990, in Danville, Virginia, having suffered from spinal cancer. His career inspired the 1977 film Greased Lightning, starring Richard Pryor in a loose adaptation of his biography.
Scott was inducted into the International Motorsports Hall of Fame and the NASCAR Hall of Fame in the 2015 class. He was also inducted into the Virginia Sports Hall of Fame in 2000, and Danville honored him with a historical marker in January 2013.
Only a small number of African-American drivers followed Scott into NASCAR Cup-level competition in the decades after his career, among them Willy T. Ribbs, Bill Lester, and Bubba Wallace. Scott's daughter Sybil became a consultant for NASCAR's diversity initiatives, and his story reached new audiences through its inclusion in the 2017 Pixar film Cars 3, where a fictionalized character named River Scott, voiced by Isiah Whitlock Jr., was based on him.