At Newlands, Edward Moore scored his maiden T20 century, hitting 101 off 58 balls with 11 fours and four sixes.
Wayne Parnell (46 off 41 balls) and Kyle Verreynne (23 off 11) provided good support as Western Province (WP) scored 208-6.
Mbulelo Budaza (3-41) was the standout bowler for the KZN Inland Tuskers.
Kagiso Rapulana scored 60 off 43 deliveries, but the Tuskers could only manage 160-7, with Keith Dudgeon (35* off 17) holding firm.
Kyle Simmonds and Juan James each took two wickets for WP.