Chasing a stiff 179, KXIP made a struggling start with openers Paul Valthaty (17) and Adam Gilchrist (9) falling cheaply inside five overs for just 31 runs before Karthik and Shaun Marsh (42) helping their side win the match with seven balls to spare with a 111-run third-wicket stand in 9.3 overs.
David Hussey (21 not out from 15 balls) finished the run chase in style with a six off Ravindra Jadeja as KXIP reached 181 for four in 18.5 overs to take his side to their fifth win in 11 matches.
Karthik smashed seven fours and five sixes in his 33-ball knock while Marsh hit five fours and two sixes from 30 balls to set up the win on a batting-friendly pitch at the Holkar Stadium which was hosting the first IPL match.
Pacer R P Singh grabbed a superb 4/25 to threaten to win the match for KTK but the KXIP batsmen were up to the task.
In Image: Kings XI Punjab batsman Dinesh Karthik celebrates his half-century
Scorecard | IPL 2011