In-form Gambhir struck a 43-ball 62, his sixth half-century this season, with six fours and three sixes while McCullum hit 37 from 29 balls with the help of four fours and a six to give Knight Riders a spectacular start.
The duo put on 99 runs for the opening wicket but KKR could not capitalise on the superb start as the middle order failed to fire once again.
From 99 for no loss in the 12th over, the Knight Riders were reduced to 128 for five in the 18th over as Jacques Kallis (4), Manoj Tiwary (12) and Yusuf Pathan (11) failed to live up to the challenge as the two-time defending champions Chennai made their way back.
In their must win match, Chennai captain Mahendra Singh Dhoni's gamble of inserting the Knight Riders in seemed to have backfired with the duo of Gambhir and McCullum putting on yet another fruitful opening partnership.
Their 99-partnership was KKR's second highest, behind 113 (vs Pune Warriors India) this season, something that put themselves in sight of a challenging total.
The Knight Riders were 86 for no loss after 10 overs but the remaining five overs proved quite fruitful for Chennai who made a stunning comeback, claiming two wickets for just 26 runs.
The opening duo made their intention loud and clear, taking charge of Chennai pace spearhead Ben Hilfenhaus.
