As a halfback at Lincoln University in Jefferson City, Missouri, Lewis was nicknamed "The Lincoln Locomotive". He set school records for touchdowns in a season (22), touchdowns in a career (64), rushing yards in a season (1,239) and career rushing yards (4,457).
CFL
After a stellar college career, Lewis signed with the Winnipeg Blue Bombers of the Canadian Football League (CFL). He was named All-Pro six times and was a member of four Grey Cup-winning Blue Bombers teams. He missed the 1956 season with a serious ankle injury. During his 11-year career in the CFL, he rushed for 8,861 yards with a 6.6 yard average. He also was a remarkable kick-returner, averaging 29.1 yards on kickoff returns in his CFL career. His career rushing total of 8,861 yards stood as a Winnipeg Blue Bomber record for 41 years until it was passed by Charles Roberts in 2007. His career totals in return yardage, and yards per carry, still stand as Blue Bombers records.
Lewis also coached golf and was a physical educations instructor at Lincoln. He was the head coach of the women's basketball team from 1981 to 1993, compiling a record of 104–206 in 12 seasons. Lewis later served as the interim athletic director at Lincoln.
Lewis was inducted into the Canadian Football Hall of Fame in 1973 and the College Football Hall of Fame in August 2005. In 2005, he was named to 20 All-Time Blue Bombers Greats, to commemorate the 75th anniversary of Blue Bombers franchise. Lewis was inducted into the Manitoba Sports Hall of Fame and Museum in 2005, was inducted into the Black College Football Hall of Fame in February 2018, and the Missouri Sports Hall Of Fame in 2019.