India posted an imposing total of 304 for six but, after the target was reduced under the Duckworth/Lewis method following rain interruptions, England cruised to 241 for four in 32.2 overs to win the series 3-0.
One match was a no-result and another was tied.
India responded well after being put into bat, Virat Kohli's fine knock of 107, including nine fours and a six, providing the backbone of a commanding total.
Rahul Dravid made a typically stylish 69 in his final one-day international and a sparkling 50 not out off 26 balls from captain Mahendra Singh Dhoni ensured the touring side chalked up a big score.
England stayed on course for their target thanks to efficient knocks of 50 by captain Alastair Cook and 63 by Jonathan Trott.
Ian Bell struck two sixes in his 26 before Ravi Bopara and Jonny Bairstow on his debut steered them home.
Bopara finished unbeaten on 37 and Bairstow, son of former England wicketkeeper David, made 41 off just 21 balls including three sixes.
