Sehwag (31), Gambhir (11), Virat Kohli (6), Yuvraj Singh (9) and Suresh Raina (18) perished in quick succession to give the visitors the upper hand in what eventually turned out to be a lop-sided contest.
Skipper Dhoni, who scored a heroic unbeaten 113 in the first ODI in Chennai, again provided some resistance with a cautious and unbeaten 54 but wickets kept tumbling at the other end to nullify his efforts.
The series defeat against Pakistan marks another low for the struggling team which suffered an embarrassing Test series debacle against England at home and levelled a T20 series 1-1.
Thursday's defeat has also rendered the third and final ODI at Ferozeshah Kotla in Delhi on Sunday inconsequential.
In Image: India's Gautam Gambhir walks off after his dismissal