The duo compiled India's best partnership against the archrivals as the tourists took their overnight total of 356 for two to 467 without further loss by lunch on the second day at the Multan stadium on Monday.
Sehwag, who ended the first day on 228, became India's highest scorer in Test cricket when he moved to 292 by lunch, beating Venkatsai Laxman's 281 against Australia at Kolkata in 2001.
Tendulkar was unbeaten on 106, his 33rd Test century surpassing retired Australian captain Steve Waugh's tally of 32 and leaving him one short of country-mate Sunil Gavaskar's world record of 34.
Sehwag, who has so far batted for eight hours and hit 38 boundaries and five sixes, is eight runs away from scoring only the 18th triple century in Test cricket.
Tendulkar's knock is studded with 14 boundaries.
The partnership, which began before tea on the first day, 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 Umer at slip and wicketkeeper Moin Khan failed to take sharp chances.
Off-spinner Saqlain Mushtaq bowled just two overs on the second day as captain Inzamam-ul-Haq kept faith in his seam bowlers.
Shoaib Akhtar went for 0-85, Shabbir conceded 0-97 and Mohammad Sami had 1-84 as the Indians revelled in their first Test on Pakistan soil since 1989.
India had won the preceding one-day series 3-2.