Robin Petersen himself scored 62 runs, but deemed that Jacques Kallis' unbeaten knock of 78 as more important in placing the Proteas just 35 runs behind the visitors at close of play.
Faf du Plessis and AB de Villiers produced 205 runs for the fifth wicket but South Africa failed to complete a historic run chase in Johannesburg.
South Africa will have to either see out 90 overs for a draw or chase down 320 runs for victory. While the former looks the more likely option for the hosts, the odds remain on India to go 1-0 up in the two-match series.
India took complete control against South Africa (138/2 in second innings) on Day 4 with the hosts staring at a huge target on a challenging pitch.
Despite Dwayne Smith's heroics, the Mumbai Indians skipper believes that the bowlers played a key role in the victory.
Dwayne Smith slammed an unbeaten half-century while Kieron Pollard scored a quick-fire 31 to help Mumbai Indians register a comfortable victory and also stay in hunt for a semifinal spot.
Head selector Andrew Hudson says Petersen is "the obvious choice" to come in for former limited-overs captain Smith, who was ruled out of the ODI tournament to have surgery on his injured left ankle.
Smith was forced to watch South African team-mate Alviro Petersen hit 167 after losing the toss on the opening day of the English County Championship First Division clash 24 hours earlier.
South Africa tucked into some valuable batting practice ahead of next week's opening Test reaching 128 for one after the second day of their three-day tour match against Australia A at the Sydney Cricket Ground on Saturday.
The Australian club registered an all-round performance to remain unbeaten in the tournament.
It will be the Delhi Daredevils' batting power up against Lions' bowling consistency.
Stuart Broad called for a repeat of the spirit of Edgbaston 2011 to ensure England manage to overturn South Africa's command of the second Test and series, as their place at the top of the world rankings hangs by a thread.
Opening batsman Alviro Petersen ground out a century as South Africa battled England's all-pace attack on the first day of the second Test at Headingley on Thursday.
Centuries from Alviro Petersen and JP Duminy tightened South Africa's grip on the series, and although New Zealand responded strongly thereafter, they face an unlikely battle to level the series with two days remaining.
New Zealand's on-field misery matched the Wellington weather as South Africa sauntered to 246 for 2 after rain accounted for almost four hours of play for the second consecutive day.
South Africa took control of a weather-disrupted opening day in the third Test against hosts New Zealand, compiling 136-2 on Friday on a wicket expected to favour the bowlers.
Top-ranked one-day batsman Hashim Amla has been dropped out of South Africa's limited-overs squad for the rest of the series against Sri Lanka because his wife is expecting their first child.
A Jacques Kallis-inspired South Africa clinched its first home series win since 2008 with a 10-wicket victory over Sri Lanka in the series-deciding third Test at Newlands on Friday.