After a troubled youth background, Lewis turned professional in June 1966 in Canton, Ohio, United States. In his debut Lewis faced "Clown Prince" Art Miller. Lewis won this fight with a 1st round knockout.He accrued 15 wins from his debut. But then Bob Stallings stopped him in seven in 1967. But Lewis won their rematch a year later by a 2nd round knock out. Lewis also fought Leotis Martin twice a while later, losing the first by KO in 9 and the direct rematch by decision. Lewis outpointed fringe contender Dick Wipperman in 1967. He fought an ageing Cleveland Williams whom he stopped in four in 1970, Oscar Bonavena against whom he lost by disqualification after decking Oscar several times in 1971 and Jack O'Halloran, against whom he lost on points in 1973.
He is best remembered for a non-title fight with Muhammad Ali which took place at Croke Park in Dublin, Ireland on July 19, 1972, which he lost by an 11th round TKO. Lewis was outclassed. Down in the 5th it looked like the end. But he rallied onwards. He then surprised many by launching offensives just when it wasn't expected, typically after an Ali burst. The Lewis-Ali event is described in the documentary film, When Ali Came to Ireland.