The Indians, trailing by 202 runs in the first innings, slumped to 149 for five in their second knock at stumps on Wednesday, still 53 away from saving an innings defeat with five wickets in hand.
Virender Sehwag stood tall among the ruins with a brilliant 86 not out, while Parthiv Patel was on 13, the pair having put on 44 for the unbroken sixth wicket.
Sehwag, who hit a majestic 309 in the first Test at Multan which India won by an innings, hit 14 boundaries in his aggressive style even as wickets tumbled at the other end.
Pakistan, who made 489 runs in the first innings following a defiant 73 from Asim Kamal, ripped through India's batting for the second time in the match on a Gaddafi stadium wicket that tended to keep low at times.
India, bowled out for 287 in the first innings, made a disastrous start when opener Aakash Chopra was dismissed for five, leg-before to Shoaib Akhtar.
Then in the last over before tea, captain Rahul Dravid was run out after a mix-up with Sehwag to leave India tottering at 15 for two.
Soon after the break, it became 43 for three when Sachin Tendulkar was trapped leg-before by a Mohammad Sami delivery which kept low.
Sehwag added 45 for the fourth wicket with Venkatsai Laxman before Umar Gul, Pakistan's bowling hero in the first innings with five wickets, struck in his fifth over.
Gul produced a late outswinger to bowl Laxman for 13.
From the other end, Sami returned for his second spell to claim first innings century-maker Yuvraj Singh caught behind for 12 to send half the Indian side back for 105.
Earlier, left-handed Asim Kamal hit a polished 73 to help Pakistan extend their lead after India's Irfan Pathan helped his team stage a fightback with a three-wicket burst.
Kamal held the innings together in the company of tailenders to ensure Pakistan secured an almost impregnable lead after Pakistan slipped from the overnight 355 for three to 386 for seven.
Kamal, who made 99 in his debut Test against South Africa last year, put on 46 for the eighth wicket with Akhtar (19) and 38 for the ninth with Gul.
Kamal, who hit three towering sixes and seven fours, was the last man out when he was caught behind the stumps by Patel off leg-spinner Anil Kumble who finished with 2 for 146.
The hosts had made a disastrous start to the day, losing four wickets in the space of 30 runs with Pathan being the main destroyer.
The 19-year-old, who took six wickets in the Multan Test, trapped captain Inzamam-ul-Haq leg-before with the sixth delivery of the day.
Inzamam did not add to his overnight score of 118 which was studded with 14 boundaries.
Two overs later, Laxmipathy Balaji forced an edge off Pakistan's vice captain Yousuf Youhana to wicket-keeper Patel.
Youhana, playing his 50th Test, made 72 with 13 hits to the fence and his departure ended Pakistan's hopes of building a huge first innings lead.
Pathan finished with 3 for 107 while Balaji took 3 for 81.