Spinner Simon Harmer took six wickets as South Africa romped to victory by 408 runs in the second Test for their first series win in India in 25 years on Wednesday.
World Test champions South Africa bowled out a dismal India for 140 in a mammoth chase of 549 on day five in Guwahati for a 2-0 Test sweep.
It is India's biggest defeat at home by runs and a fifth loss in seven home Tests, having been whitewashed 3-0 by New Zealand last year.
Off-spinner Harmer, 36, returned figures of 6-37 as South Africa clinched a Test series in India for only the second time, the first in 2000 under Hansie Cronje.
Ravindra Jadeja resisted with 54 before Keshav Maharaj had him stumped and the spinner soon got the final wicket of Mohammed Siraj, with Marco Jansen pulling off a stunning catch in the deep.
India lost the opening Test in Kolkata inside three on a pitch with uneven bounce before South Africa once again beat the hosts in their own game of spin on a batting-friendly track.
The visitors declared their second innings on 260-5 on day four to hand India a record chase but the hosts batting once again failed and they never threatened to get close.
India rode their luck early in the day when Jansen had Sai Sudharsan caught behind but the delivery was declared a no-ball after the bowler overstepped. The batter was on four.
In the next over another overnight batter Kuldeep Yadav survived a reprieve on four when Aiden Markram dropped him at first slip off Harmer.
But the relief was short-lived for India as a relentless Harmer soon bowled Kuldeep for five for the first wicket of the day.
The off-spinner then dismissed Dhruv Jurel, for two, three balls later and soon sent back skipper Rishabh Pant for 13 as India slumped to 58-5.
The batters fell like nine pins on a pitch where South Africa posted 489 after they elected to bat.
India were bundled out for 201 to concede a first-innings lead of 288 but South Africa did not enforce the follow-on and decided to bat again.
Left-arm quick Jansen returned figures of 6-48 in India's first innings after the bowler hit a quickfire 93 with the bat.
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South African all-rounder Senuran Muthusamy led the batting charge with his 109, his maiden Test century.