England, at lunch, were 126 for two. They needed a further 374 runs to reach a victory total of 500, a target way in excess of the current Test record fourth innings winning score of 418 for seven set by the West Indies against Australia in Antigua in 2003.
But their two star batsmen were still at the crease.
England captain Michael Vaughan, dropped by India counterpart Rahul Dravid on 18, was 22 not out and Kevin Pietersen 17 not out.
England resumed on 56 without loss. Andrew Strauss was 23 not out and Alastair Cook 27 not out.
The left-handed openers survived some testing early overs Monday from left-armer Zaheer Khan and fast bowler Shanthakumaran Sreesanth.
But Rudra Pratap Singh, India's other left-arm swing bowler, eventually ended a first-wicket stand worth 79 in the 12th over of the day.
The accurate Singh struck with his fourth ball Monday when he persuaded Strauss, without a Test hundred in over a year, to fend an outswinger on 32 and VVS Laxman made no mistake with the second slip catch.
Veteran leg-spinner Anil Kumble, a thorn in England's side this match with both bat and ball, then removed Cook with a clever piece of play.
The 22-year-old's fondness for playing off his pads has become something of a weakness this series and India captain Rahul Dravid set two close catchers behind square on the on-side when the Essex batsman was facing Kumble.
India's unusual field-placing was rewarded when Cook, on 43, saw a genuine glance well caught low down by Laxman at short backward square-leg to leave England 86 for two.
Vaughan almost fell to Kumble but the normally reliable Dravid dropped the first slip chance with England 113 for two.
India, 1-0 up after a seven-wicket win at Trent Bridge following a gutsy draw at Lord's, were on the verge of making history.
If they avoided defeat they would become only the third India side, after their 1971 and 1986 predecessors, to win a Test series in England in 15 tours dating back 75 years.
England needed an unlikely victory to maintain a six-year unbeaten run in home Test series, encompassing eight wins and three draws in 11 campaigns, since losing the 2001 Ashes.
India had all but ensured against defeat by scoring 664 in their first innings - their record Test total against England - which included Kumble's unbeaten 110, his maiden Test century in 118 matches at this level and the only one by an India batsman in this series.
Kumble then became Test cricket's third most successful bowler outright, overtaking retired Australia quick Glenn McGrath's mark of 563 wickets, when he had Monty Panesar lbw to end England's first innings on 345 all out.