Kuldeep Yadav followed up his match-winning 5-24 from the first T20I at Old Trafford with 6-25 from 10 overs as the hosts were bowled out for 268.
Rohit Sharma, meanwhile, hit a second-straight century of the tour, following his T20 ton at Bristol with an unbeaten 137 in the run chase.
England had begun brightly on the same ground that they hammered 481 against Australia and were 71-0 at the time of Kuldeep's introduction after 10 overs.
The left-arm wrist spinner proceeded to take three wickets in his opening two overs and, despite Jos Buttler and Ben Stokes rebuilding the England innings with a stand of 93, Kuldeep went on to claim their scalps too.
In reply, India cruised to their target with eight wickets and almost 10 overs to spare as Sharma and captain Virat Kohli (75) impressed.
India, who have already won the T20 series 2-1, can take victory in the three-match series at Lord's on Saturday.