Batting at number six, Pandya struck a brilliant 59 not out off 28 balls that rescued the home team from a compromising position of 78-4 in the 12th over to post 175-6 in their 20 overs.
Lungi Ngidi and Lutho Sipamla had put India in early trouble with Ngidi eventually finishing with figures of 3-31 in four overs while Sipamla took 2-38.
The Proteas then could not cope with a disciplined India bowling attack as the visitors were dismissed for a paltry 74 all out, their lowest total in T20Is.
The highest individual score came from Dewald Brevis, who made 22, with only three other players reaching double-figures.
Pandya also contributed with the ball, grabbing the key wicket of experienced middle-order batter David Miller for a single.
The heavy defeat will be disappointing for the Proteas, as they look to get their combinations right ahead of the T20 World Cup early next year.
The second match of the five-match series takes place in Chandigarh on Thursday.
India top-order batter Ishan Kishan has been ruled out of the second T20I in New Zealand due to a groin strain, with teenage star Vaibhav Sooryavanshi poised to return to the starting XI.
South Africa produced a dominant performance to beat Australia by an innings and 31 runs in the second Test at St George's Park in Gqeberha on Thursday, levelling the series at 1-1.
South Africa produced a commanding performance to defeat Australia by an innings and 31 runs in the second Test at St George's Park in Gqeberha, with captain Temba Bavuma leading the way with a magnificent 179.
India earned their highest-ever T20I run chase when they successfully chalked off New Zealand's 225/4 with four wickets remaining in a run-soaked encounter in Christchurch on Thursday night.
