South Africa set India a mammoth victory target of 549 in the second test and reduced the hosts to 27-2 to stay firmly on course for a 2-0 series sweep in Guwahati on Tuesday.
A first-innings lead of 288 had put the world test champions in the box seat, and they declared their second innings on 260-5 immediately after Tristan Stubbs was dismissed for 94 midway through the final session.
India finished 522 behind and needing to bat out three sessions on Wednesday to eke out a draw.
Sai Sudharsan will resume on two with night-watchman Kuldeep Yadav on four.
Stubbed said he was "a little bit" disappointed to fall short of a hundred. "They are two-down, so I'll take that," the batter said.
"We had forty minutes after lunch. Thought I'll give it a go (for the hundred)...If you were just looking to defend, I thought you'll be a sitting duck."
Earlier, South Africa's top order looked ill at ease against the turning ball after resuming on 26 for no loss in the first ever test at Barsapara Cricket Stadium in Northeast India.
Ryan Rickelton (35) and Aiden Markram (29) added 59 for the opening stand before left-arm spinner Ravindra Jadeja (4-62) removed both.
Rickelton was snared at cover, while Markram was done for by a delivery that drifted in from wide of the crease and spun past the bat to peg back the off stump.
Off-spinner Washington Sundar had South Africa captain Temba Bavuma caught at leg slip for three and would have claimed the wicket of Stubbs had Rishabh Pant not missed a stumping opportunity. Pant is leading the home side in the absence of injured India captain Shubman Gill.
Tony de Zorzi (49) fell short of a fifty, pinned lbw by Jadeja, but Wiaan Mulder, who made 35 not out, and Stubbs consolidated South Africa's position.
Jadeja bowled Stubbs, ending a fine knock that included nine fours and a six, and Bavuma declared immediately.
Faced with a mountain to climb, India faltered early in their second innings.
Opener Yashasvi Jaiswal (13) upper cut Marco Jansen for a spectacular six but fell caught behind in the fast bowler's next over trying to play another cut shot.
His opener partner KL Rahul made six before spinner Simon Harmer rearranged his stumps with a delivery that turned significantly.
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