England, with the majority of their T20 World Cup squad not involved, had thrashed Ireland at the same venue on Monday, with the hosts skittled out for just 45.
It was a very different story in a rain-marred third ODI when Ireland made 155-7 in reply to England's 153 all out.
England seemed poised to complete a series sweep when Ireland started the last over, bowled by Mady Villiers, needing eight to win but lost three wickets.
Alana Dalzell, however, hit a four off the last ball to take Ireland to their first ODI win over England since 2001.
"We just tried to keep the camp in positive spirits," Ireland captain Gaby Lewis, who made 72 before falling in the 19th over, told the BBC.
"Cricket's hard sometimes and obviously playing against top-quality nations, these kind of defeats are going to happen, but I think it's the way we can bounce back and I think we did that brilliantly."
Rain reduced the match to 22 overs per side and England were then bowled out for 153 -- despite 52 off 42 balls from the in-form Tammy Beaumont -- as Ireland's Aimee Maguire took 5-19.
"It's been three good games of cricket," said stand-in England skipper Kate Cross.
"Credit to Ireland, I thought they were the better side today."
