Eoin Morgan will captain England's One-Day International team for the one-off game against Ireland and for the five-match series against Australia that follows.
Regular captain Alastair Cook, Twenty20 International captain Stuart Broad and fast bowler James Anderson have all been rested for the six matches.
Ian Bell and Graeme Swann are also given time off after their involvement in all five Ashes Test matches with Kevin Pietersen, Joe Root and Jonathan Trott rested from the Ireland ODI but included in the squad to take on Australia.
Uncapped pace bowlers Jamie Overton and Boyd Rankin are included in both squads along with batsman Michael Carberry while Chris Jordan and Gary Ballance have an opportunity to impress against Ireland.
James Taylor, who made his ODI debut against Ireland two years ago, is in the squad to travel to Dublin but misses out on the squad for the Australia series as Pietersen, Root and Trott return.
Left-arm spinner Danny Briggs travels to Ireland while the more experienced off-spinner James Tredwell is preferred for the home fixtures with wicket-keeper Jos Buttler and all-rounder Ben Stokes in both squads.
England take on Ireland in Dublin on 3rd September - a fixture which will have special resonance for former Irish internationals Morgan and Rankin - before the first ODI against Australia in Leeds is on 6th September.
"Following a very intense period of cricket this summer we have decided to rest a number of senior players which will allow them to recover from a heavy workload over the last three months and to prepare for the tour of Australia which begins in eight weeks," National Selector Geoff Miller said.
"This creates an excellent opportunity for players who have impressed in county cricket and for England Lions recently to test themselves at international level as we continue to build a squad ahead of the ICC Cricket World Cup which is less than 18 months away.
"There are a number of very experienced one day players in the squad alongside players who are new to international cricket and we are expecting a very tough challenge both from a strong Ireland side and then from Australia in what will no doubt be a very competitive NatWest series."
Ireland named uncapped Eddie Richardson in their squad last week while Australia picked uncapped leg-spinner Fawad Ahmed in their squad earlier in the month.
Morgan has captained England in one previous ODI and three Twenty20 Internationals. In 2011, he led a similarly experimental England side to an 11-run win over Ireland.
After a string of injuries to team-mates he captained England in two Twenty20 Internationals in India in December, winning one and losing one before leading England against New Zealand earlier this summer to a five-run defeat.
England ODI squad v Ireland: Eoin Morgan (captain), Gary Ballance, Ravi Bopara, Danny Briggs, Jos Buttler, Michael Carberry, Steven Finn, Jamie Overton, Boyd Rankin, Ben Stokes, James Taylor, James Tredwell, Luke Wright
England ODI squad v Australia: Eoin Morgan (captain), Ravi Bopara, Jos Buttler, Michael Carberry, Steven Finn, Chris Jordan, Jamie Overton, Kevin Pietersen, Boyd Rankin, Joe Root, Ben Stokes, James Tredwell, Jonathan Trott, Luke Wright
© Cricket World 2013