Buttler struck a brilliant career-best 131 off 64 balls, his second century T20I hundred, while captain Harry Brook contributed a 45-ball 95 not out as England posted a a mammoth 257-3 in their 20 overs.
It was hell-raising day for the India bowlers and fielders as Buttler and Brook put on a partnership of 233 for the second-wicket after the early loss of opener Phil Salt in the second over.
Having dominated the previous three contests, England set out to work to defend the target with an expected India with the bat.
Ishan Kishan struck a brisk 56 while Tilak Varma contributes a quick-fire 53 as India eventually ended on 201-8 in 20 overs.
Sam Curran was the lick of the England bowlers after left-arm seamer took 3-36 while leg-spinner Adil Rashid finished with figures of 2-24.
After being outplayed in the shortest format, India will have to lift themselves with a three-match ODI series starting in Birmingham on Tuesday.
Shreyas Iyer is still looking for his first win since becoming India's T20I captain but says the challenging start will make him a better player and leader in the future.
India T20I captain Shreyas Iyer admitted his team is going through a transition period after losing to England by nine wickets to surrender the series 3-0.
England secured a series-winning nine-wicket victory in swashbuckling style against India in the fourth T20I in Bristol on Thursday.
The proposed Euro Nations Cup has encountered a significant obstacle after the England and Wales Cricket Board (ECB) declined to support plans for the tournament's showpiece match to be staged at Lord's.
