After India spinners restricted England to a modest 201/9, opener Smriti Mandhana (53 retired hurt), Mithali and Deepti Sharma (54 not out) ensured that the hosts crossed the line with 4.4 overs to spare.
India had won the first match by one wicket while England had levelled the series after they defeated the hosts by eight wickets in the second game.
But India eves today dished out a clinical performance with both the bat and ball.
For England, wicket-keeper Amy Jones (94) top scored but she failed to find partners. Indian spinners wreaked havoc on English batters, as they shared six wickets, while veteran pacer Jhulan Goswami (2-39) too chipped in.
But Mithali was the cynosure of eyes at the Vidarbha Cricket Association Stadium here as she punished English bowlers, hitting nine boundaries.
After losing the T20 tri-series, which also involved Australia apart from England, and the ODI series to the Southern Stars, India finally found the winning momentum against England.
Brief Scores: England Women 201/9 in 50 overs (Amy Jones 94, Heather Knight 36, Rajeshwari Gaikwad 2-32) lost to India Women 202/2 in 45.2 overs (Mithali Raj 74 not out, Deepti Sharma 54 not out, Anya Shrubsole 2-37) by eight wickets.
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