It was Ireland's sixth successive Test defeat since becoming a full member of the International Cricket Council in 2018, while Sri Lanka registered their 100th Test victory after dominating the contest.
Beaten by a record innings and 280 runs in the opening Test, also at Galle, Ireland put up their highest total of 492 on a batting-friendly track with Paul Stirling making 103 and Curtis Campher smashing 111.
Skipper Andy Balbirnie (95) and stumper Lorcan Tucker (80) also made significant contributions though both missed out on a hundred.
Left-arm spinner Prabath Jayasuriya was pick of the Sri Lankan spinners claiming 5-174 in the first innings.
Sri Lanka racked up a mammoth 3-704 before declaring the first innings with opener Nishan Madushka (205) and top-order batsman Kusal Mendis (245) smashing double centuries.
Skipper Dimuth Karunaratne (115) and former captain Angelo Mathews, who made 100 not out, also helped themselves to easy hundreds.
Heading into the final day's play at 2-54, Ireland could not force a draw despite Harry Tector's defiant 85 and were all out for 202.
Jayasuriya, who reached 50 Test wickets in only his seventh Test, was player of the match for his haul of seven wickets.
Mendis bagged the player of the series award for making 385 runs across two innings.
"We have to take the positives. To take it to day five was excellent. We know how good a team Sri Lanka are," Balbirnie said.
His counterpart Karunaratne was relieved to wrap up victory before rain could interrupt play.
"We knew it could rain anytime, so I asked the bowlers to put in a good session and the bowlers put their hands up," he said.
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