The visitors lost despite fighting half-centuries by Ajinkya Rahane (86) and Wriddhiman Saha (77 not out) who made a gallant effort to try and take India to victory after a top order collapse.
Chasing a stiff 307-run target for victory, Rahane and Saha by tea had brightened India's chances of registering a series win with an unbeaten 160-run stand for the sixth wicket after they were struggling on 18 for five at one stage.
India A had won the first 'Test' by an innings and 13 runs at Rustenburg.
They were cruising on 177 for five at tea with both Rahane and Saha at the crease before the tables completely turned around after the break with the visitors losing five wickets for just seven runs.
Rahane's dismissal triggered the collapse as the tailenders caved in meekly.
Even as Saha tried hard to put up a brave fight but he kept losing partners at the other end. He remained unbeaten on 77 off 183 balls including 11 boundaries.
Hendricks finished with figures of 6 for 27 from 17 overs, while Simon Harmer chipped in with three for 79.
Earlier, resuming the day on three for one, India lost four wickets in quick succession for just 17 runs, as Hendricks struck three early blows.
Cheteshwar Pujara, who resumed today on 2, failed to add to his overnight total as Jutin Ontong ran him out.
Hendricks, who dismissed opener Murali Vijay (2) yesterday, accounted for the other three wickets -- overnight batsman Shahbaz Nadeem (5), Dinesh Karthik (0) and Ambati Rayudu (1) -- to leave the Indians in tatters, before Rahane and Saha came to the team's rescue.
Both Rahane and Saha played with a lot of caution and made sure that the Indians do not lose any more wickets. The duo frustrated the host bowlers by completing their fifties.
But just after the tea, Hendricks got the breakthrough for his team by sending back Rahane for a well-made 156-ball 86, studded with 10 fours.
Saha tried his best to keep one end intact but quickly ran out of partners.
Unfortunately for India, barring Rahane and Saha, no other batsmen could reach the double-figure mark.
Along with Hendricks, Harmer saw off the tail in virtually no time to bundle India all out for 185 in their second innings.
Stuart Binny (4), Parvez Rasool (1), Ishwar Pandey (0) and Siddarth Kaul (0) failed miserably even as Hendricks and Harmer wreaked havoc.
Earlier, India's first innings had folded for a meagre 201 in reply to South Africa's 341. In the second essay the Proteas declared at 166 for five to set the visitors a stiff target.