As a running back at Lincoln University Lewis was nicknamed the "Lincoln Locomotive". Lewis holds the 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).
After a stellar college career, Lewis signed with the Winnipeg Blue Bombers of the Canadian Football League. He was named All-Pro six times and eventually earned a spot in the Canadian Football Hall of Fame. Lewis was a member of an amazing four Grey Cup winning Blue Bombers teams. 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. Bud Grant, legendary Blue Bombers' (and later head coach of the Minnesota Vikings), considered Leo Lewis the best player he had ever coached, whether in Canada or the United States. Lewis was voted one of the CFL's top 50 players (#29) in a poll conducted by Canadian sports network TSN.
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 Bomber records.
He had three children, two of whom played professional gridiron football (one for the Minnesota Vikings - Leo Lewis III - and the other for the USFL Denver Gold and Oakland Invaders and the CFL's Ottawa Rough Riders and the Calgary Stampeders - Marc Lewis).