Jayasuriya, 36, announced last week he would be retiring from Test cricket after the series against Pakistan to make room for Sri Lanka's next generation of Test openers.
Fans had been hoping for one last match-winning display from the most prolific batsman in Sri Lanka's history, a man adored for his dare-devil approach, in the second Test.
Jayasuriya failed in the first innings, scoring 14, and dislocated his right thumb while taking a catch yesterday, his 74th catch and final act in Test cricket.
The dislocation was so bad that the bone jutted out of a deep cut and Jayasuriya clicked the joint back into place himself before being rushed to hospital in Kandy.
Jayasuriya's status in Sri Lanka is such that his arrival at the hospital created a frenzy.
Waiting patients were cleared out of the casualty ward to make space. Doctors and surgeons rushed to see if the injury could be patched up for a final appearance in Sri Lanka's second innings.
After four stitches were inserted, doctors advised the team's management that Jayasuriya would play no further part in the match and would be out of action for at least four weeks.
But with Sri Lanka precariously placed overnight on 73 for eight, Jayasuriya requested a pain-killing injection before the start of the third day's play.
The left-hander had returned to win a one-day game against India last year after dislocating his shoulder in the game, and this time he had to be persuaded out of attempting one last heroic innings.
''I tried my best to bat and I took an injection in the morning, the doctors were not keen at all on me going out there,'' Jayasuriya told journalists. ''It was totally disappointing for me - I got injured and we lost the match.'' Pakistan won by eight wickets and took the series 1-0.
Jayasuriya is the holder of the highest individual score by a Sri Lankan, the 340 he scored in Colombo against India in 1997.
He started his career as a middle order batsman in 1991 and took over as an opener after smashing an exhilarating hundred against Shane Warne and Glenn McGrath at Adelaide in 1996.
He went on to score 6,613 runs at 41.59 in 102 Tests, hitting a total of 14 hundreds. He also claimed 92 wickets at 33.18 with his left-arm spin.
''Sanath has been a fantastic cricketer, an absolute credit to the game of cricket and a wonderful ambassador for Sri Lanka's cricket,'' Pakistan's coach Bob Woolmer told journalists.
''It is always sad when someone who has done so much for cricket on the field has to pack up his bags and stop.
''But as he walks away he can be proud that many people all around the world are sad to see him go - cricket will be poorer without him,'' Woolmer added.
Jayasuriya, a former captain, will now concentrate on one-day cricket until the 2007 World Cup, after which he has announced he will retire.
His contribution to one-day internationals has been 10,053 runs at 31.90 and 297 wickets in 357 matches.
He was named Most Valuable Player of the Tournament during the 1996 World Cup which he helped Sri Lanka win with his ferocious assaults against the new ball.
''Sanath was responsible with Ramesh Kaluwitharana of revolutionising the one-day game during the 1996 World Cup with his audacious batting,'' Woolmer said.
Sri Lanka's captain Mahela Jayawardene echoed Woolmer's sentiments. ''Sanath is a cricketing legend - we are just all so sad it ended like this. We so wanted to give him a special farewell,'' Jayawardene told Reuters.