Kuldeep Yadav celebrates with Virat Kohli after taking the wicket of S.Africa's Jean-Paul Duminy on Wednesday. Reuters
South Africa captain Faf du Plessis won the toss and batted but a superb double strike by Jasprit Bumrah left his side reeling.
India leg-spinner Yuzvendra Chahal then took four wickets in a meagre total of 227 for nine.
India, with Rohit Sharma, dropped early in an innings of 122 not out — the highest individual score of the tournament to date —took their time over the chase before winning with 15 balls to spare.
India's spinners plunged South Africa deeper into trouble in their World Cup match in Southampton on Wednesday, backing up paceman Jasprit Bumrah, who did the early damage.
Earlier, leg-spinner Yuzvendra Chahal struck twice in one over, grabbing the prized scalp of skipper Faf du Plessis for 38 to leave the Proteas in desperate trouble.
Chahal bowled Rassie van der Dussen for 22 with the first ball of his second over to end a 54-run third-wicket partnership for South Africa.
The wrist spinner then bowled Du Plessis to send a crowd dominated by Indian fans wild.
Spin partner Kuldeep Yadav also chipped in with the wicket of JP Duminy, trapping the batsman lbw for three as South Africa slipped to 89-5.
South Africa inched their way to 112-5 at the end of the 28th over, with David Miller and Andile Phehlukwayo battling on.
South Africa, who desperately need a win to keep their campaign alive after two successive defeats, saw their openers depart early in Bumrah's first spell.
Bumrah, the world's top-ranked one-day international bowler, had the ball darting around on a cloudy morning in Southampton as he sent back Hashim Amla for six.
Amla, who missed South Africa's previous match against Bangladesh, defended a delivery with extra bounce from Bumrah but got an outside edge that was caught at second slip by Rohit Sharma.
Bumrah then struck again in his next over, with Quinton de Kock, who made 10, edging to skipper Virat Kohli at third slip, meaning South Africa were two down for 24.
South Africa have been hit by a spate of injuries, with pace spearhead Dale Steyn making an early exit from the tournament without playing a game.
India, among the tournament favourites, are playing their first game in the round-robin event that concludes on July 14 in London.
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The Board of Control for Cricket in India (BCCI) had defended Dhoni after he sported a dagger logo on his green gloves in India's win over South Africa on Wednesday.
"We are feeling sad, and you can see me, I feel like crying," said office worker Neeraj Singh, sobbing, after New Zealand's dramatic 18-run win. "We love Team India, we love Kohli, we love Mahi (MS Dhoni) and forever we will love cricket. And like our boss Kohli has said, Dhoni will forever be our captain in our hearts," he said.
Hyderabad got off to a faltering start as they lost David Warner just 10 runs on the board. He holed out to Udana off Washington Sundar.
Seven-time UAE champion trainer Doug Watson combined with Sam Hitchcott to steal the show with a hat-trick while Salem Bin Ghadayer and Royston Ffrench enjoyed a double.
To win the targeted trophy, a team must feature in the top four of the IPL 2020 points table.
Delhi’s dismal run in the tournament thus continues, which leaves them on 14 points -- behind Royal Challengers Bangalore (RCB) -- who too have same number of points, but are second, courtesy of a better net run rate.