England, in their second innings, were 54 for two when the day's second rain interruption led to tea, a lead of 151 in the opening match of this three-Test series.
But given that James Anderson had earlier taken a Test-best five for 42 as India were dismissed for a lowly first innings 201, it remained to be seen if the tourists' star-studded batting line-up could offer better support to the bowlers second time around.
England captain Michael Vaughan was three not out and Kevin Pietersen seven not out as India's seamers thrived in overcast conditions.
Left-arm quick Khan, who at tea had figures of two for 23 in 9.4 overs, had Andrew Strauss defensively edging to first slip Sachin Tendulkar following a 110-minute rain break.
England, who lost wickets in quick succession following a rain interruption on Friday, then saw 40 for one become 43 for two when Alastair Cook, their other left-handed opener, was lbw to a ball that swung back into him.
Anderson, playing his first Test since January's final Ashes clash in Sydney and his first at home since 2004, helped England make light of the absence of injured quicks Matthew Hoggard, Stephen Harmison and Andrew Flintoff after they had collapsed to 298 all out.
He was well-supported by Ryan Sidebottom, who returned to Test cricket after a six-year gap earlier this season, with the left-arm swing bowler taking four for 65.
India, who'd resumed on 145 for four, lost their last six wickets Saturday for 46 runs in 90 balls.
Anderson, whose previous Test best of five for 73 also came at Lord's, during his debut against Zimbabwe in 2003, added Sourav Ganguly to a list of wickets that already included fellow Rahul Dravid, the India captain, and Tendulkar.
Left-hander Ganguly, who scored a hundred at Lord's in his Test debut 11 years ago, was clean bowled for 34 by a full, swinging delivery.
And with his fifth ball Sidebottom had nightwatchman RP Singh skying to Anderson at mid-off for 17.
Hard-hitting wicket-keeper Mahendra Singh Dhoni, a ball after hesistantly guiding Anderson just short of the slips, was out for nought when a similar shot carried to Ian Bell at third slip.
Sidebottom's inswinger did for Anil Kumble before VVS Laxman, the last of the recognised batsmen, was caught behind for 15.
But it was Anderson, rejuvenated by plenty of overs for Lancashire and the input of new England bowling coach Allan Donald, the former South Africa quick, who won the 'race' to five wickets when Khan's miscued hook lobbed to first slip Strauss.
Anderson's final figures of five for 42 in 24.2 overs contained just three boundaries.
It was the third time he'd taken five wickets in an innings in his 17-Test career but the first since his debut season.