Dublin-born Eoin Morgan will captain for the first time in the one-day game against Ireland on 25 August.
Selector Geoff Miller said: "I know he is very much looking forward to developing his leadership credentials while in charge of a young squad."
Uncapped quartet James Taylor, Jonathan Bairstow, Ben Stokes and Scott Borthwick are named in a 13-man squad after impressing for England Lions.
England play India in a one-day series after the match in Dublin.
Morgan, 24, who is the vice-captain of England's Twenty20 team, played for Ireland in the 2007 Cricket World Cup, before pledging his future to is England in order to play Test cricket, and making one-day debut for them against West Indies in May 2009.
He has made four ODI centuries - the first for Ireland against Canada in 2007, and three for England - against Bangladesh, Australia and Pakistan.
England have been captained by an Irishman before - Frederick Fane was born in County Kildare in 1875 and led England in an Ashes series in Australia in 1907/08.
The four new additions have all stepped up from the England Lions team that beat Sri Lanka A 2-1 in a three-match one-day series.
Leicestershire's Taylor, 21, has been in superb recent form, scoring two centuries against Sri Lanka A.
Wicketkeeper Bairstow, 21, is the son of former England Test player David Bairstow, while Durham's New Zealand-born batsman Stokes, 20, and his leg spinner county colleague Borthwick, 21, also get a chance to impress.
Miller added: "By resting several players that have played international cricket since the start of the summer the opportunity has arisen for a number of talented up and coming players to continue their development on the international stage.
"We know from previous encounters that Ireland are a tough ODI outfit and we'll be fielding a very strong England side that will need to play well."
Jonathan Trott is included in the squad despite missing the last two Test matches against India with a shoulder injury.
England's regular ODI captain Alastair Cook is rested, along with Kevin Pietersen, Ian Bell, Stuart Broad, Graeme Swann and James Anderson.
Team director Andy Flower has also been given time off so assistant coach Richard Halsall will stand in.
Ireland will be aiming to repeat their shock win over England at the World Cup earlier this year.
England squad for one-day match against Ireland on 25 August:
Eoin Morgan (captain), Jonathan Bairstow, Ravi Bopara, Scott Borthwick, Jade Dernbach, Steven Finn, Craig Kieswetter, Graham Onions, Samit Patel, Ben Stokes, James Taylor, Jonathan Trott, Chris Woakes.