Pakistan, trailing by 376 runs on the first innings, were shot out for 245 in their second knock soon after lunch on the fourth day on Friday to suffer their second innings defeat of the series, won 2-1 by Sourav Ganguly's India.
Left-hander Asim Kamal played a lone hand for the hosts with an unbeaten 60 despite batting in extreme pain due to a swollen elbow caused by a hit while fielding at short-leg on Wednesday.
Kamal's heroic effort helped the last five Pakistan wickets add 151 runs after the top five had been bundled out for 94.
India had won the first Test at Multan by an innings and 52 runs before Pakistan drew level with a nine-wicket triumph at Lahore last week.
India's heroes were vice-captain Rahul Dravid, whose monumental 270 fired the tourists to 600 in reply to Pakistan's modest 224, and seamer Laxmipathy Balaji who took four wickets in the first innings and three in the second.
Leg-spinner Anil Kumble, who claimed four of the last five wickets on Friday, finished as the most successful bowler in the series with 15 wickets. He now has an overall tally of 397 wickets from 84 Tests.
It was a remarkable double for Ganguly's men on their first major tour of Pakistan since 1989, having won the preceding One-day series 3-2.
India's first overseas series victory since Sri Lanka in 1993 also made Ganguly his country's most successful Test captain, surpassing the previous record of 14 wins by Mohammed Azharuddin.
Of India's 21 away wins since it started playing Test cricket in 1932, eight have come in the last four years under the team management of Ganguly and his deputy Dravid.
Pakistan's batting crumbled for the second time in the match during the morning session which was extended by 30 minutes due to Friday prayers.
The hosts, who resumed at the overnight score of 49 for two, found it tough to negotiate the Indian seamers in overcast conditions at the Rawalpindi stadium.
Nightwatchman Kamran Akmal (23) hit three boundaries in Balaji's opening over, but failed to survive his second when the paceman sent the off-stump cartwheeling.
Captain Inzamam-ul-Haq and Yasir Hameed also did not last long despite surviving dropped catches by Dravid and Kumble in the slip cordon.
Hameed made 20 when he edged Ashish Nehra down the leg-side and wicketkeeper Parthiv Patel dived to his left to pick up a low catch.
Inzamam edged Balaji's outswinger to Patel as Pakistan slipped to 94 for five in the first hour.
Yousuf Youhana and Kamal put on 81 for the sixth wicket before Youhana offered a tame return catch to Kumble after making 48.
Kumble then dismissed Mohammad Sami first ball of his next over, but Shoaib Akhtar denied the leg-spinner a hat-trick and celebrated that with three boundaries and a six in the same over.
Akhtar, who did not bowl on Thursday because of a side strain, hammered 28 off 14 balls before holing out in the deep against Kumble soon after lunch.
Kumble also removed Fazl-e-Akbar, before Sachin Tendulkar brought up India's win by the dismissal of last man Danish Kaneria.