After being put in to bat first by England, the Indians struggled to score and were held at 185 for six in their 50 overs. In reply, England reached the target with five wickets and four balls to spare to take a 2-0 lead in the five-match series.
Mithali was once again the backbone of India's batting as she played out a fine 73-run knock to give some respectability to the Indian scorecard.
However, the skipper did not get much support from her other team-mates, who found the going tough against the an excellent spell by spinner Isa Guha, who took four wickets conceding 29 runs in her 10 overs.
Indian openers Karuna Jain (14) and Rumeli Dhar (28) made a good start and took the visitors to 44 before Guha struck twice within nine runs to break the partnership.
Karuna was the first to go holing out to Charlotte Edwards and the England skipper then accounted for Dhar (28) again off Guha's bowling Their departure saw Mithali and Anjum Chopra (12) combine in a 40-run partnership for the third wicket before seamer Laura Newton struck to dismiss Chopra.
Hemlata Kala (30) joined Mithali and the duo revived the innings with an 84-run partnership but Guha returned to dismiss the duo.
The English managed to hold the visitors at 185 for six and fine contributions by Sarah Taylor (40), skipper Edwards (47) and Jenny Gunn (42) saw the hosts clinching the match without much trouble.
Caroline Atkins opened the batting with Laura Newton but the partnership was broken pretty soon as Newton was dismissed by Preeti Dimri for 12.
Later, Atkins and Sarah Taylor combined to take the score past fifty but Atkins' (24) fall to Dimri and Taylor's departure at 40, to Nooshin Al Khader gave the Englsih a scare.
However, Edwards and Gunn went about scoring with ease and put up a stand of 78 before the captain departed, stumped by Karuna off Dimri's bowling. But Gunn held the innings together and guided her side, alongside Beth Morgan, to victory.
England won the opening one-dayer at Lord's and the second match in Sheley had to be suspended owing to bad weather.
Brief Scores: India: 185 for six in 50 overs (Mithali Raj 73, Isa Guha 4/29) England: 186 for five in 49.2 overs (Charlotte Edwards 47, Jenny Gunn 42, Preeti Dimri 2/25)