Khan's return of four for 59 in 21 overs, his best against England, came as the hosts were bowled out for 198, with India needing fewer than 11 overs on Saturday to wrap their opponents' first innings.
At lunch India were 40 without loss, a deficit of 158.
Openers Dinesk Karthik (20 not out) and Wasim Jaffer (15 not out) came through 16 testing new-ball overs in conditions that had offered early assistance for swing and seam bowling provided the ball was pitched up.
But well though Ryan Sidebottom, on his Nottinghamshire home ground, James Anderson and Chris Tremlett bowled, they couldn't take a wicket.
That left England contemplating the prospect of having to bowl to the likes of India's star-studded middle order, featuring captain Rahul Dravid, former skipper Sourav Ganguly and VVS Laxman, in conditions that were becoming increasingly good for batting.
Khan's haul improved upon the four for 79 he took during the second innings of the drawn first Test at Lord's where India clung on with one wicket standing before bad light and rain cut short play on Monday's final day.
Anil Kumble, the only other India bowler used on Saturday, took three for 32 in 12.3 overs.
England started the second day on 169 for seven, all their top order batsmen out, with India's seam attack exploiting helpful conditions for swing bowling following Dravid's decision to field first after a wet outfield meant no play was possible before lunch on Friday.
Tremlett, dropped on four, resumed on 16 not out with Sidebottom unbeaten on nought.
Kumble posed problems for Tremlett, who made a pair on his debut at Lord's and, in Saturday's fifth over, he bowled him for 20 as he misread a quicker, straighter delivery and played for turn instead.
But Khan, who last season was the second most successful bowler in English first-class cricket with 78 wickets for Worcestershire, had Monty Panesar edge full length delivery to Laxman for one.
Kumble then wrapped up the innings when he bowled Anderson for one with Sidebottom 18 not out.
England Ist innings 198 (Cook 43, Ian Bell 31, Collingwood 28; Zaheer 4 for 59, Kumble 3 for 32, Sreesanth 1 for 16, Ganguly 1 for 11) Vs India 40/0 (Karthik 20 n o, Jaffer 15 n o).