Trescothick, who missed the three-Test series in India this year after abandoning the tour for undisclosed personal reasons, recovered from his usual leaden-footed start to strike 106 in an imposing England total of 318 for three at the close.
It was his 14th Test century, this third against Sri Lanka and his second at Lord's.
Trescothick was ably assisted by Andrew Strauss, who scored 48 before he was caught a minute before lunch and 21-year-old Alastair Cook who helped the Somerset left-hander add 127 for the second wicket.
Cook, who scored a century in his Test debut as a late replacement for Trescothick, again showed astonishing maturity, this time in the unaccustomed position of number three, scoring 89 before he was caught behind from a tired stroke.
The batsmen were assisted by a pitch containing no hidden demons and a Sri Lanka attack comprising of two bowlers with more than 900 Test wickets between them and a further three with a grand total of 25.
Sri Lanka had packed the side with batting, leaving their attack woefully exposed on a hot day before a capacity crowd relishing the chance to watch England in their first home Test since capturing the Ashes at the Oval last September.
Chaminda Vaas, with 301 Test victims at the start of play, was unable to obtain significant movement either in the air or off the pitch and it was left to Muttiah Muralitharan, second in the all-time list with 611, to impose any kind of restraint on the England batsman.
MURALITHARAN STRIKES
Muralitharan, playing his first Test at world cricket's headquarters, twirled his off-spin from both ends after he was introduced into the attack 25 minutes before lunch.
He had one good shout for lbw against Trescothick turned down by umpire Rudi Koertzen then picked up the wicket of Strauss caught at slip by Mahela Jayawardene from the first delivery of the final ball of the morning session.
Trescothick brought up his 50 with a hearty sweep off Muralitharan for six. He then clumped two fours off Farveez Maharoof's innocuous medium pace before surviving another lbw appeal from Muralitharan which television replays suggested would have struck the stumps.
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After playing himself in with almost exaggerated concentration, Pietersen started to enjoy himself on the ground where he made a memorable debut in a losing cause against Australia last year.
He drove Muralitharan off the back foot for four through the covers then danced down the pitch to hit a lofted on-drive into the evening shadows at the Pavilion End.
Sri Lanka took the new ball, which merely gave Cook the chance to push Maharoof through the covers for a boundary then take an all-run four with a similar shot which stopped just before the ropes.
Pietersen slashed Vaas twice through the off-side to reach his sixth Test half-century with nine fours from 93 balls in only 61 minutes. He was then caught at short cover by Jehan Mubarak off Maharoof, to find to his relief that it was the hapless Sri Lankan's 11th no-ball of the innings.
Maharoof gained some consolation when Cook played an airy drive in the same over and was caught behind by Kumar Sangakkara. He had struck 11 fours from 184 balls.
