Leg-spinner Lewis captured five for 25 off 9.4 overs as the home team, chasing 232 off 50 overs, were dismissed for 198.
West Indies' 33-run victory in their 13th match on tour was also highlighted by Shivnarine Chanderpaul's 81 off 102 balls.
Chanderpaul and Daren Ganga, who made 40, featured in a second-wicket stand of 101 against a Western Province XI comprising reserves and six emerging non-white youngsters.
The match was played in Langa in the Cape Town suburbs and several white companies took corporate facilities on a rare visit to a township.