England scored 9-305 in reply to Sri Lanka's 6-321, which included a century from captain Kusal Mendis in a high-scoring clash on Thursday during which Buttler had looked to be taking England to a comfortable triumph before damaging his hamstring.
He retired hurt on 67, but as Sri Lanka pulled themselves back into the contest with key wickets, a limping Buttler came back to the crease, with England needing 20 runs off the last two overs.
He was, however, only able to add two more runs before being caught at deep mid-wicket, with his dismissal effectively ending home hopes.
England had needed only 63 off their last 10 overs to seal the series but were pinned back by the Sri Lankan bowlers, who got their side over the line for their first success of the tour after suffering a 3-0 whitewash in the Twenty20 internationals.
Sri Lanka skipper Mendis won the toss and elected to bat, leading from the front as he scored 121 and shared a second-wicket partnership of 137 with Kamindu Mendis, who made 54.
Kusal Mendis was dropped on 17 by Gus Atkinson at fine leg in an expensive slip off Jamie Overton's bowling and had another life one run short of his century when he was given out caught behind off Overton but reviewed immediately, only for the TV umpire to confirm there had been no nick.
He then cover drove the next ball to complete a seventh ODI century.
Pavan Rathnayake added 48 off 39 balls before being run out, and Janith Liyanage contributed 32 before becoming Jofra Archer's only wicket as the England paceman returned expensive figures of 1-65.
England's reply began in impressive fashion. They took advantage of sub-standard Sri Lankan bowling, allowing Tom Banton and Ben Duckett to put together an opening stand of 143 inside the opening 20 overs.
But almost out of nowhere, left-arm spinner Dunith Wellalage bowled Duckett (67) and had Banton stumped for 73 off 61 balls, before trapping captain Harry Brook for a single. He finished his 10 overs with figures of 3-49.
Buttler turned the tide in England's favour again before his injury, but stretching to complete a run, he looked to suffer a torn muscle.
England won the first ODI by 89 runs at Chester-le-Street on Tuesday, and the decider will be at The Oval in London on Sunday.
