The lanky speedster, whose consistency has always been under the scanner, delivered when it mattered most, as he grabbed a career-best 7 for 74 to bowl out the home team for a 223 in pursuit of a competitive victory target of 319.
From a relatively comfortable 173 for four, the last six wickets fell for only 50 runs with the final five coming in only 12.2 overs after lunch on an absorbing fifth day's play.
It took 28 long years for India to win a Test match at the 'Home of Cricket' after 'Kapil Dev's team achieved the feat back in June 1986 winning by five wickets.
It also marked Mahendra Singh Dhoni's first significant victory as Test captain outside the sub-continent. The last time India won a Test match outside the South Asian region was back in 2011 when they defeated West Indies in a 1-0 series win.
The victory was achieved in the 89th over when James Anderson tapped a Ravindra Jadeja delivery towards short cover and set off for non-existent single but Jadeja was alert enough to pick up and break the stumps down with a direct throw triggering off instant celebrations.
Skipper Dhoni as usual collected a stump as souvenir as the jubilant players hugged each other with the support staff and reserve bench applauding them from the hallowed balcony.
Resuming at a precarious 105 for four on the final day, the two overnight batsmen Joe Root (66) and Moeen Ali (39) batted with a lot of determination adding 101 runs in 44.4 overs before Ishant struck at the stroke of lunch.
He got one to rear up awkwardly as left-hander Ali took his eyes off the ball in order to fend it. The ball lobbed up at short leg for Cheteshwar Pujara to complete a simple catch.
Then came a series of horrible pull-shots as each and every England batsmen took the bait of pulling Ishant and were holed out in the process. Matt Prior (12) deposited the mistimed pull to Murali Vijay specifically stationed at deep mid-wicket boundary for that shot.
Ben Stokes (0) completed a hat-trick of ducks as he provided a skier which Pujara accepted gleefully. Root, who looked solid in defence then pulled straight down Stuart Binny's throat at deep square leg.
Once Stuart Broad (8) gloved one down the leg side to Dhoni, Ishant broke Amar Singh's 78-year-old record by recording the best bowling figures by an Indian at the 'Mecca of Cricket'. He had taken 6 for 35.
Interestingly, this is also India's first Test win since the retirement of legendary Sachin Tendulkar as India have drawn three and lost two in the five Tests since the iconic cricketer's retirement in November 2013.
Ironically, when England lost to India at the Lord's back in 1986, it brought down curtains on David Gower's captaincy as Mike Gatting was put in the hot seat in place of the elegant left-hander.
It seems like 'Yesterday Once More' for the home team skipper Alastair Cook's head is on line after prolonged poor form with the bat as well as his lack of assertiveness while captaining the side.
For the Indian captain Dhoni, it will be one of his happiest moments having received a lot of flak for losing eight Test matches overseas in England and Australkia during the 2011-12 season.
The turning point was the last over before lunch when Ishant broke the deadlock removing Moeen Ali.
Moeen (39) was sorted out with a rising delivery, which he fended awkwardly to be caught by Cheteshwar Pujara at short leg. This was after a fighting 101 run stand for the fifth wicket with Joe Root (52 batting), who is again looking good for a big score.
Ishant (3-47) was in fact smashed for 13 runs in the previous over Root, who struck three of his five boundaries in that single over. While Root has faced 126 balls so far, Ali played 147 balls hitting five fours. The duo defied Indian bowlers for close to 45 overs (44.4 overs).
Earlier, the first session belonged entirely to the two English batsmen as they started the day at the overnight score of 105/4. Play began under overcast skies and floodlights were switched on as well but that didn't deter Root or Ali.
They had used the heavy roller on the morning pitch and perhaps it helped calm the pitch down a little bit. Even so, the bowling was tight as they gave away only 35 runs in the first 16 overs.
But as the batsmen got set the runs started flowing, 68 runs off 30 overs coming in the session then as the target went down.
To their credit, the two batsmen never presented any straight-forward chance to the Indians, grinding their bowling attack. Dhoni tried many different ploys as he does but it didn't help matters as the 150-run mark came up in the 70th over.
Root then shifted gears and started stroking some quick boundaries to bring up his fifty off 122 balls, in the 74th over of the innings, while in the very next, the 100-run partnership between the two batsmen also came up.
However disaster struck once Moeen was removed minutes before the break and the match took a decisive turn.
Ishant Sharma bowls India to victory as England crumble
Ishant Sharma claimed seven wickets to bowl India to a 95-run victory over England in the second test at Lord's on Monday, their first overseas win since 2011.
India's second victory at the home of cricket and first since 1986 continued England's miserable year after series defeats by Australia and Sri Lanka.
Resuming at 105 for four in pursuit of 319, Joe Root and Moeen Ali survived until the final ball before lunch when the latter fell to Sharma.
The willowy right-armer claimed four more wickets after the break as England's batsmen capitulated in the face of India's short-pitched barrage and were bowled out for 223, putting the visitors 1-0 up in the five-match series.
Sharma finished with career-best figures of 7-74, including five wickets in 33 balls.
Root and Moeen had earlier given hope of an unlikely home victory, having come together with England in trouble at 72 for four midway through Sunday's evening session.
They added a further 68 runs on Monday morning before Moeen, who batted for a day to nearly save the second test against Sri Lanka at Headingley last month, fell last to a brute of a delivery from Sharma which forced him to fend off to Cheteshwar Pujara at short leg.
Root and Prior came out after lunch bristling with intent, hitting 20 runs in the first two overs after play resumed as Mohammed Shami and Sharma offered a procession of short balls.
Captain Mahendra Singh Dhoni's plan paid dividends shortly afterwards, however, when Prior, who has endured a poor run both behind the stumps and with the bat, hooked Sharma to Vijay at deep mid-wicket for 12.
Ben Stokes completed a pair in the match, mis-hitting Sharma to Pujara at mid-on and Root went the same over for 66, caught by Stuart Binny after another poor hook shot.
Sharma claimed his fifth victim of the day and seventh of the innings when he had Stuart Broad caught down the legside by Dhoni.
James Anderson was last to fall, run out by Ravindra Jadeja.
The third test starts in Southampton on Sunday.