The Olympic super-heavyweight champion grabbed a premature victory after just 43 seconds of round two with a powerful left.
Bookmakers made Harrison a 33-1 odds-on favourite for the bout and boxing fans will surely hope this is the last time he is matched against such an inferior opponent.
Lewis had come to Britain with a flattering record of 10 knockout wins out of 14 fights but his one-round loss to Dominick Guinn in June quickly appeared more appropriate.
He was dropped three times before the contest was waved off early in the second round as Harrison boosted his knockout percentage.
Harrison's debut in the north-west had been dogged by the usual criticism and on the night it hardly got off to the most auspicious of starts.
The arena's fire alarm forced him to curtail his initial ring walk and when he made his second attempt there was a small smattering of boos among the audience.
Lewis' first act was to lunge in with a hopeless sweeping right-hand but it was to prove one of the only punches he threw in the fight.
Harrison typically took some time to size up his opponent but quickly discovered that he could land almost at will.
The bell saved him from a first-round defeat but the end was always in sight.
Harrison smashed home another big left which dropped Lewis again and looked like putting him out.
But the American was nothing if not game and he clambered up for more punishment.
Another fast right-left combination knocked him down for the third time and brought referee Marcus McDonnell's timely intervention.
Hare's classy win
It was hard to see what Harrison could possibly have gained from such a futile exercise - apart from regaining confidence in his knockout power after being stretched to points in his previous two contests.
But at least Harrison got rid of the man in front of him and moved up another notch on his painfully slow rise towards professional prominence.
Meanwhile, there was more British success as James Hare successfully defended his Commonwealth welterweight title in Huddersfield.
Hare had too much class for Zimbabwe's Farai Musiiwa and had him on the canvas with a big right in the fourth round, although the referee decided he had slipped.
But Hare continued to land telling punches and ended the contest in the eighth round when he put Musiiwa down twice.