Sehwag and the dour Aakash Chopra put on 160 for the first wicket as the tourists moved from the lunch score of 104-0 to 228 for two by tea on the opening day of the Multan Test on Sunday.
Stand-in captain Rahul Dravid, who elected to take first strike in good batting conditions, fell cheaply for six, but Sachin Tendulkar kept Sehwag company at tea on 17.
Sehwag smashed the Pakistani bowlers around the Multan cricket stadium, hitting 20 boundaries and five sixes in his sixth Test century from 21 matches.
Delhi team-mate Chopra proved the perfect foil at the other end, making 42 before being caught in the leg-trap off Saqlain Mushtaq.
Dravid top-edged a hook off Mohammad Sami to square-leg, finally giving Pakistan captain Inzamam-ul-Haq something to smile about on his home ground.
Pakistan were unlucky not to see Sehwag's back just before lunch when Sami put down a skier at mid-wicket off Saqlain.
Saqlain himself dropped Sehwag soon after the break when he failed to latch on to a low catch at mid-on off Shoaib Akhtar.
Sehwag, 76 at lunch, reached the coveted three-figure mark in fitting style, guiding the express pace of Akhtar over third man for his fourth six.
He had earlier launched the historic Test series by flicking his second delivery from Sami to the square-leg boundary.
The swashbuckling opener smashed Shabbir Ahmed over third man for six and brought up his half-century by hitting Akhtar for his ninth boundary.
Chopra, who was on nine when Sehwag reached 50, finally made an impact when he flicked Akhtar for his first four.
Both teams went in with three seamers and one spinner on a grassless wicket that promises to throw up a lot of runs.
The Indians, without injured skipper Sourav Ganguly, left out Murali Kartik and Ajit Agarkar from the 13 named on Saturday. Leg-spinner Anil Kumble joined the attack with seamers Zaheer Khan, Irfan Pathan and Laxmipathy Balaji.
Pakistan preferred Saqlain to leg-spinner Danish Kaneria.