Jonny Bairstow put Ireland to the sword by smashing 82 off 41 balls but England had to overcome a middle-order wobble before sealing a series victory at the Ageas Bowl.
After Adil Rashid had taken 3-34 to reach 150 one-day international wickets and help restrict Ireland to 9-212, Bairstow equalled the record for the fastest fifty in this format by an Englishman off 21 balls.
Bairstow, skipper Eoin Morgan (0) and Moeen Ali (0) were dismissed within six balls as England lurched from 3-131 to 6-137, before an unbroken 79-run stand between Sam Billings and David Willey helped the hosts to their target with four wickets and 17.3 overs to spare.
The pair had been the stand-out performers in Thursday's opener and came to the rescue here, Billings finishing on 46 not out while Willey followed up his 2- 48 with an unbeaten 47 in the evening sunshine.
Ireland were once again grateful for Curtis Campher, who followed up his unbeaten 59 on his international debut 48 hours earlier with a mature 68, the linchpin in the tourists' batting after they had won the toss.
But the final match of the series on Tuesday will be a dead rubber, even though Campher also chipped in with a couple of wickets on a day Reece Topley made his England return after a four-year hiatus because of injury, taking 1-31.
Morgan was full of praise for opener Bairstow after his match-winning knock.
"We've a lot of guys who can do that at the top of the order," Morgan told Sky Sports.
"It takes the wicket out of the equation and takes the game away from the opposition.
"We lost wickets in the chase, but the way the guys played, Jonny was outstanding at the top and Sam Billings finished it off again."
Ireland captain Andy Balbirnie added: "We made similar errors and needed our middle and lower again to get us to a relatively defendable total.
"We gave it a good crack in the field but were ultimately short and those four or five early wickets again didn't help."
Australian Associated Press