New cap Morne Morkel followed up with three wickets as India limped to 183 for eight at lunch in reply to South Africa's first innings of 328.
On a heavily overcast morning on Thursday, the batsmen struggled against the South African fast bowlers but Tendulkar and VVS Laxman appeared to have weathered the early storm before Ntini struck 40 minutes into the day.
Tendulkar was out for 63 when he appeared to change his mind and played a cramped cut shot to a ball that was going over his stumps, feathering a catch to wicketkeeper Mark Boucher.
Two balls later Ganguly took his eyes off a lifting ball and spliced a simple catch to Herschelle Gibbs at gully.
Tendulkar and Laxman had taken their fourth wicket partnership to 64 but the double strike reduced the tourists to 125 for five.
Mahendra Singh Dhoni batted aggressively for 34 as he and Laxman put on 54 for the sixth wicket.
Dhoni hit seven fours in a 39-ball innings before he played one extravagant stroke too many and edged an attempted cut off Morne Morkel to AB de Villiers at second slip. It was Morkel's first Test wicket.
Morkel struck again in his next over when Anil Kumble flashed at a wide ball and edged a catch to Boucher. He picked up another wicket when Zaheer Khan was caught at short leg in the last over before lunch.
The day started well for India, resuming on 103 for three, when Tendulkar, who was 46 not out overnight, reached his first Test half-century of 2006 with an elegant off-drive against Ntini.
It was his 14th innings since his previous substantial score, 109 against Sri Lanka in Delhi in December 2005.
Umpire Mark Benson had to leave the field with heart palpitations four overs into the day. He was taken to hospital for tests.
His replacement, South African Ian Howell, was called on to make a decision with the first ball bowled at his end when Laxman, on 11, hooked at Ntini and the South Africans went up in a unanimous appeal for a catch behind. Howell gave the batsman not out.
South Africa Ist innings 328 Vs India Ist innings 183 for 8 (Sachin Tendulkar 63, VVS Laxman 28, M S Dhoni 34, Jaffer 26; Ntini 3 for 41, Morkel 3 for 55, Nel 2 for 47)