South Africa were set 152 off 15 overs because rain delayed play for almost an hour after India had been sent into bat and made 180-7 off 19.3 overs.
Hendricks fell short of a half century but his 49 runs off 27 balls proved the basis for success to allow South Africa to go ahead in the three-match series after Sunday’s opening clash in Durban was washed out.
South Africa scored 154-5 to secure victory with seven balls remaining with Andile Phehlukwayo hitting a six to finish off the contest.
India were put into bat on a fast track and lost their first wicket after three balls as David Miller took a flying catch at square leg off Marco Jansen to see Yashasvi Jaiswal back without scoring.
But Miller dropped a similar catch two balls later, which allowed Tilak Varma to go on and score 29, but not before India were reeling at 6-2 when Shubman Gill was trapped leg before in the second over.
South Africa did not press home their advantage as wayward bowling allowed India to score briskly, with skipper Suryakumar Yadav hitting 56 off 36 balls while Rinku Singh was 68 not out off 39 balls.
Singh’s innings was brought to a premature end three balls short of the 20 overs when the umpires took the teams off for rain and the 55-minute delay meant South Africa were set a reduced target.
South Africa lost their first wicket with 42 runs on the board when Matthew Breetzke was run out for 16 but Hendricks kept calm to strike eight boundaries and keep the hosts ahead of the required run rate.
India, however, put the brakes on as they took three wickets in 10 balls to reduce South Africa to 108-4 but David Millar and Tristan Stubbs put on 31 runs for the next wicket to make all but sure they would take a 1-0 lead in the series.
The last T20 clash is on Thursday at the Wanderers in Johannesburg, after which the two teams play three one-day internationals and then two tests.
