Despite a maiden ODI half century from Faf du Plessis (60 from 94 balls), and sensible cricket from JP Duminy (52), the Proteas only managed to post 220, after losing 6 wickets for just 20 runs in the final powerplay overs.
Earlier in the innings, India's opening bowler Zaheer Khan caused problems for SA captain Graeme Smith, who nearly edged the seamer three times in the opening over.
Smith persevered however, to end with a hard fought 43 off 79 balls, and eventually fell to spinner Harbajhan Singh, who had him caught by Virat Kohli.
At the other end, Hashim Amla looked in good form, but unusually played a reckless drive to a Khan delivery, which he missed completely, leaving him minus an off-stump and on his way for just 13.
Relative newcomer Colin Ingram also looked out of sorts, in particular against the slower bowlers, and he was to fall for just 10 runs to an excellent slip catch by Kohli off the bowling of the ever-threatening Harbajhan Singh.
AB de Villiers holed out in deep midwicket after skying a long hop from Yusuf Pathan, with Zaheer Khan making a diving effort to take the catch. South Africa's talisman was also only able to make 16 of 32 balls, an indication of how slow the Newlands wicket played.
A solid partnership of 110 runs between du Plessis and Duminy steadied the ship, but once they both fell the run rate slowed again, as Wayne Parnell was run out for just 5 after a promising pull shot to start his innings.
Some late runs from tailenders Johan Botha (9) and Dale Steyn (5) helped the South Africans to their partially defensible total of 220, although India will be confident of knocking off the runs for a consecutive win.
The pick of India's bowlers included Zaheer Khan, who finished with impressive figures of 3 wicket for 43 in 9.2 overs, Harbajhan Singh who stifled the batsmen to produce 2 wickets for just 23 runs in his 9 overs, and Munaf Patel, who finished with 2 wickets for 40 runs in his 10 overs.
Scoreboard
South Africa innings
G. Smith c
Kohli b Harbhajan 43 H. Amla b Khan 16 C.
Ingram c Kohli b Harbhajan 10 A. de Villiers c Khan b Pathan 16
J-P. Duminy b Khan 52 F. du Plessis c Kohli b Patel
60 J. Botha b Khan 9 W. Parnell run out
5 D. Steyn c Raina b Patel 5 M. Morkel not out
0 L. Tsotsobe run out 0
Extras (w-4)
4
Total (all out, 49.2 overs) 220
Fall of wickets: 1-31 2-49 3-83 4-90 5-200 6-202 7-207 8-216 9-219 10-220
Bowling: Khan 9.2-0-43-3 (w-2), Patel 10-1-42-2, Nehra 7-0-42-0 (w-1), Harbhajan 9-1-23-2 (w-1), Pathan 6-0-27-1, Yuvraj 6-0-30-0, Rohit 1-0-5-0, Raina 1-0-8-0.