South Africa reached tea on 25 for one after they dismissed India, who won the toss and chose to bat, for 414.
Medium pacer Pollock took four for 75, while debutant left-arm spinner Harris claimed four for 129.
India resumed on 254 for three, and they lost their fourth wicket in the eighth over of the day when fast bowler Dale Steyn uprooted VVS Laxman's off-stump to bowl him for 13.
Sachin Tendulkar and Sourav Ganguly shared 68 for the fifth wicket before Harris had Tendulkar caught by Jacques Kallis at slip for 64 with a delivery that turned sharply out of the rough.
Tendulkar's composed innings included 11 fours and came off 130 balls.
Virender Sehwag, who was demoted to number seven after struggling at the top of the order in the first two tests, was out for an increasingly aggressive 40 when he pulled at a delivery from Harris and was caught by Makhaya Ntini at deep backward square leg.
That reduced India to 395 for six, and in all the visitors lost their last five wickets for 19 runs.
Ganguly, who was struck a fearsome blow on the helmet by Steyn with the third ball he faced, was last out for 66 when he skied a delivery from Pollock to Hashim Amla at mid-off.
Graeme Smith began South Africa's reply in spectacular style when he hooked the first ball of the innings, bowled by left-arm fast bowler Zaheer Khan, over the fine leg boundary for six.
Fast bowler Shanta Sreesanth struck back for India in the fourth over before tea when he had AB de Villiers caught behind off the inside edge by wicketkeeper Dinesh Karthik for one.
Smith was 21 not out at tea with Amla on three.