The opening fixture in Chester-le-Street was washed out, leaving India without a single victory in the five-match series.
After being put in to bat, England posted a formidable 257/3 in their 20 overs, thanks to a record-breaking 233-run partnership between Jos Buttler and captain Harry Brook.
England suffered an early setback when Prasidh Krishna dismissed Phil Salt for eight in the second over.
However, Buttler and Brook responded with an aggressive counterattack, adding 233 runs for the second wicket — the second-highest partnership for any wicket in a men s T20I between Full Member nations.
The stand ended in the penultimate over when Shivam Dube dismissed Buttler, who smashed a magnificent 131 off just 64 balls, including 12 fours and eight sixes.
Dube struck again in the same over to remove Jacob Bethell for a golden duck, but Brook remained unbeaten after an explosive 95 off 45 deliveries, hitting four fours and eight sixes.
For India, Dube claimed two wickets, while Krishna took one.
Chasing a daunting target of 258, India were restricted to 201/8 despite fighting half-centuries from Ishan Kishan and Tilak Varma.
Kishan top-scored with 56 from 35 balls, while Varma made a brisk 53 off 25 deliveries, featuring three fours and four sixes.
Captain Shreyas Iyer scored 28, Sanju Samson made 27 and Dube added 14, but the rest of the batting line-up failed to provide meaningful support.
Sam Curran starred with the ball for England, taking 3/36 in four overs. Adil Rashid picked up two wickets, while Liam Dawson, Josh Tongue and Jofra Archer claimed one wicket each.
The victory sealed an emphatic series triumph for England, while India finished the tour without a win after the opening match was abandoned due to rain.
