England threatened to pull off a famous victory only for India to seal the series with a five-wicket win on the fourth day of the fourth Test in Ranchi.
Shoaib Bashir took two wickets in two balls just after lunch to leave India five down and 72 runs short of their target of 192.
But Shubman Gill made a chanceless unbeaten 52, sharing an unbroken stand of 72 with Dhruv Jurel, who ended 39 not out.
India had earlier been cruising, only to lose three wickets for 16 runs. Yashasvi Jaiswal skewed Joe Root to James Anderson to be out for 37, Rohit Sharma edged Tom Hartley behind on 55 and Rajat Patidar was out to Bashir for a duck.
Scoring stopped, tension rose and England's belief grew. When Bashir pulled off his double strike, the prospect of an England win began to feel like a reality.
Instead India take an unassailable 3-1 lead and stretch a proud unbeaten home record that dates back to 2012, while England suffer their first series defeat under Ben Stokes' captaincy.
There is a break of more than a week before the fifth and final Test in Dharamsala begins on 7 March.
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England left to rue small margins
This was a captivating conclusion to a superb Test in what has been a wonderful series. When Rohit and Jaiswal were making untroubled progress to 82-0 there was no sign of the drama that would follow.
England were excellent on Monday, buzzing around in the field in an attempt to recapture the initiative they surrendered on Sunday.
Ultimately, they were left with too much to do. Even with the pitch playing tricks, and Bashir and Hartley belying their lack of experience, England were halted by the calmness of Gill and Jurel.
Like in their defeats in the second and third Tests, England can reflect on the moments of missed opportunity in this game.
Stokes' side gave away their final three first-innings wickets for six runs and lost 5-23 in their second. Ollie Robinson's crucial drop allowed Jurel to score 31 more runs on Sunday morning. How England would have loved to add 50 more to India's target.
Instead, they suffer their first series loss in two years and, after draws with New Zealand and Australia, England have gone three series without a win.
Bashir almost bowls England to victory
Shoaib Bashir celebrates a wicket
Shoaib Bashir took eight wickets in what was only his second Test match
Bashir is one of the most inspired England selections in recent memory. After picking up his first five-wicket haul in the first innings, he almost took England to victory in the second - bar the occasional change of end, he bowled for all of the fourth day.
From 40-0 overnight, Rohit and Jaiswal scored quickly in the opening half an hour. Rohit clipped Anderson for six and England shuffled their bowlers. Root's flight deceived Jaiswal and Anderson athletically took a diving catch at backward point.
Bashir and Hartley were employed in tandem. Hartley took the edge of the advancing Rohit and Ollie Pope held a fine catch at backward short leg to dismiss the struggling Patidar.
Gill and Ravindra Jadeja survived until lunch, only for Jadeja to pat a Bashir full toss to Jonny Bairstow at mid-wicket and, next ball, Sarfaraz Khan was caught at short leg.
Runs were almost impossible to score - India went 31 overs without a boundary off the bat. Jurel almost miscued Hartley to point, while the ball regularly scuttled low or turned past the edge.
India clung on. Bashir and Hartley switched ends, England constantly shuffled the field, but when Gill hit Bashir back over his head for six, the game was up.
Gill went past 50 with another maximum in the same over and Jurel hit the winning runs from the next.
India youngsters see them through
India's Shubman Gill and Dhruv Jurel walk off after victory
Dhruv Jurel's 129 runs (pictured right) in this Test is the most by an Indian wicketkeeper in India since MS Dhoni's 224 runs v Australia in Chennai in 2013
Even with their formidable home record, this will feel like a significant series win for India, who have come from 1-0 down without a number of established stars.
Virat Kohli, Mohammed Shami and Rishabh Pant have missed out entirely, KL Rahul has played only one Test and Jasprit Bumrah was rested for this match. In their place, Jurel, Gill and Jaiswal have stood up.
It was Jurel who led India's fightback from 177-7 in the first innings. The wicketkeeper's 90, in only his second Test, gave India momentum upon which their spinners capitalised on the third afternoon.
And Jurel's arrival calmed India on Monday. He formed a match-winning partnership with Gill, who began with uncertainty but grew in stature after lunch.
Jurel's drive for four off Bashir, from the 36th delivery he faced, broke England's hold on the game. Both men used their feet, often just to defend.
Gill faced 119 balls before his first boundary, the first of the sixes off Bashir. It was a performance of grit, determination and iron-will to seal India's 17th successive home series win.
'England out-skilled' - what they said
England captain Ben Stokes: "It was a great Test match. The scoreline says India win by five wickets but I don't think that gives enough credit to sum up the game as a whole.
India captain Rohit Sharma: "It has been a very hard-fought series. To come out on the right side after four Tests feels really good. A lot of challenges have been thrown at us but we responded pretty well."
Ex-England batter Mark Ramprakash: "England played their part, boosted by Joe Root's gritty century, but ultimately they were out-skilled in these conditions."
