Abhishek's sensational 135 off 54 balls was the highest T20I score ever by an India batter and was hailed by defeated captain Jos Buttler as one of the best knocks he'd ever seen.
Chasing a mammoth target of 248 on Sunday, England opener Phil Salt (55 off 23) started well but had little support as wickets tumbled around him. Indian spinners took early wickets, leaving the visitors stumbling at 4-68.
England then collapsed spectacularly to 97 all out in 10.3 overs with Mohammed Shami claiming three wickets and Varun Chakaravarthy, Shivam Dube, and Abhishek taking two apiece.
"This is the best I've bowled, but a lot of scope to improve, there were a few bad balls, I should not have bowled them," player of the series Chakravarthy said.
"It was just the matter of bowling the right ball at the right time, that's what I was working on."
Put in to bat, Abhishek's onslaught propelled India to their highest powerplay score of 95, studded with 16 boundaries.
"We were really outplayed," Buttler said. "I've played quite a lot of cricket and credit to Abhishek Sharma. That was one of the best T20 knocks I've been on the receiving end of.
"You always sit down and think what more could we have done or how we could have stopped him, but some days I think you have to give a lot of credit to the opposition. He played brilliantly well."
Brydon Carse managed to stem the run flow, claiming the wickets of Tilak Varma and out-of-form captain Suryakumar Yadav in his successive overs, while Dube was sent back to the pavilion in the third over of his spell.
Tilak and Dube's cameos provided vital support to Abhishek but Suryakumar's poor run of form continued as he was caught out for two, ending his series with just 28 runs.
Apart from Carse, Mark Wood, who replaced Saqib Mahmood, bowled a fiery spell and chipped in with two wickets of Sanju Samson and Hardik Pandya.
Abhishek was the toast of the Mumbai fans. "It's a special one, coming for the country, always a great feeling. When I see it's my day, I always try to go from the first ball," he said.
India will next play three one-dayers against England from February 6.
