The left-arm paceman was appearing in his first ODI since being left out of England's World Cup-winning squad for Jofra Archer.
And he responded by taking 4-12 inside four overs as Ireland slumped to 28-5 after losing the toss in a match that launches the new World Cup Super League, which will determine qualification for the 2023 50-over showpiece in India.
Given the first over by England captain Eoin Morgan, Willey need just four balls to have Ireland dangerman Paul Stirling chipping an inswinger to the skipper at midwicket.
And Ireland were 7-2 when captain Andy Balbirnie was caught behind driving at Willey.
Ireland ODI debutant Harry Tector was then bowled for a nine-ball duck by Saqib Mahmood.
Gareth Delany hit five fours in his 22 before he struck Willey straight to Tom Banton at backward point.
And next ball the 30-year-old Willey, the son of former England batsman and umpire David Willey, had Lorcan Tucker lbw for a duck on review to leave Ireland in dire straits at 28-5 inside seven overs.
The three-match series is being played behind closed doors.
As happened before each of the recent England-West Indies Tests, players from both sides took a knee before play in support of the Black Lives Matter campaign.
The match is England's first home ODI since beating New Zealand in a dramatic Super Over in last year's World Cup final at Lord's.
England's red and white-ball fixtures are overlapping in a season cut short by the coronavirus outbreak and they are maintaining two separate squads, meaning a clutch of World Cup winners including Joe Root, Ben Stokes and Archer will not feature against Ireland.
But England's side on Thursday featured several familiar faces including Jason Roy, Jonny Bairstow and Adil Rashid, as well as Morgan.
Ireland's team included veteran all-rounder Kevin O'Brien, whose stunning century set up a remarkable win over England during the 2011 World Cup in Bangalore.