Sehwag struck a monumental 309 and Tendulkar an unbeaten 194 to lift India to a record 675 for five on Monday before stand-in captain Rahul Dravid declared an hour before stumps on the record-shattering second day.
Pakistan, needing 476 to avoid a follow-on, closed the day at 42 for no loss with Imran Farhat on 17 and Taufiq Umer on 20.
India's highest total against Pakistan, surpassing the 539 for nine declared at Chennai in 1961, set the stage for an Indian domination of their first Test on Pakistani soil since 1989.
Sehwag batted for nine hours and hit 39 boundaries and six sixes to join a select band of 17 batsmen who have scored triple centuries in Test cricket. Australia's Don Bradman achieved the feat twice.
The swashbuckling 25-year-old opener was finally dismissed in the post-lunch session when a tired edge off Mohammad Sami was caught in the slips.
Tendulkar's 33rd century surpassed retired Australian captain Steve Waugh's tally of 32 and left the Indian champion just one short of country-mate Sunil Gavaskar's world record of 34.
Tendulkar was six runs away from his fourth double-century when Dravid ended the run feast in a bid to put pressure on the tired Pakistanis.
Sehwag and Tendulkar, who came together before tea on the first day, put on 336 for the third wicket to compile India's best partnership against Pakistan.
The stand bettered the previous record of 200 achieved by two pairs against Pakistan: Gavaskar and Kris Srikkanth at Chennai in 1987 and Ravi Shastri and Sandeep Patil in Faisalabad in 1984.
Pakistan's bowlers, who struggled for the second successive day on the lifeless track, were let down further by poor catching close to the wicket.
Sehwag, who was missed twice on the first day, escaped twice in one Shabbir Ahmed over on the second morning when Taufiq at slip and wicketkeeper Moin Khan failed to take sharp chances.
Off-spinner Saqlain Mushtaq then missed a simple return catch when Tendulkar was on 176.
India, who resumed at the overnight score of 356 for two, reached 467 without further loss by lunch and moved to 588 for four at tea as Sehwag and Tendulkar launched into the hapless bowlers.
Sehwag, who had publicly aired his desire to go for a triple hundred after ending the first day on 228, reached the landmark soon after lunch by lofting Saqlain over the long-on ropes for his sixth six.
Venkatsai Laxman, whose Indian record of 281 against Australia at Calcutta in 2001 was overtaken by Sehwag, managed only 29 when he was run out by a superb throw from the fence by Yousuf Youhana.
Left-handed Yuvraj Singh, replacing the injured captain Sourav Ganguly for the match, then hit a quickfire 59 before his dismissal signalled the declaration.
Saqlain was the most expensive Pakistani bowler, finishing with 1-204 from 43 overs. Express paceman Shoaib Akhtar went for 0-119, Shabbir conceded 0-122 and Sami returned with 2-110.
India won the preceding One-day series 3-2.