Martin Johnson has recalled regular starters Ben Foden, Chris Ashton, Mike Tindall, Shontayne Hape and Toby Flood in the backs, as well as Dan Cole, Courtney Lawes and Nick Easter in the pack as England look for a repeat of last weekend's win over the Welsh.
Saracens scrum-half Richard Wigglesworth, Wasps hooker Steve Thompson, Leicester lock Louis Deacon and back-row duo Tom Wood and Hendre Fourie are also given a chance to press their World Cup claims in Cardiff.
Only wing Mark Cueto and prop Alex Corbisiero remain from the 23-19 win at Twickenham for what is England's final game before the deadline for World Cup squad announcements on August 22.
Lions tourist Lee Mears is named on the bench but there is bad news for fellow Lion Ugo Monye who doesn't feature for the second week running.
As for Ireland, Declan Kidney has brought back a trio of Lions for the first of their back-to-back games with the French in Bordeaux.
Keith Earls and Ronan O'Gara are both included in the back division, while Donncha O'Callaghan is named at lock following the last-gasp 10-6 defeat to Scotland a week ago.
Eoin Reddan joins O'Gara at halfback, with Cian Healy, Rory Best and Mike Ross forming an all-new front row, Donnacha Ryan moving from the second row to the blindside flank and Sean O'Brien starting at openside.
Lions skipper Paul O'Connell is included among the replacements, as is Jamie Heaslip and inexperienced Munster scrum-half Connor Murray, but Brian O'Driscoll is still not ready to return from a neck and shoulder complaint.
England (vs Wales, Saturday, kick-off 2.30pm)
Ben Foden (Northampton); Chris Ashton (Northampton), Mike Tindall (Gloucester, capt), Shontayne Hape (London Irish), Mark Cueto (Sale); Toby Flood (Leicester), Richard Wigglesworth (Saracens); Alex Corbisiero (London Irish), Steve Thompson (Wasps), Dan Cole (Leicester); Louis Deacon (Leicester), Courtney Lawes (Northampton); Tom Wood (Northampton), Hendre Fourie (Sale), Nick Easter (Harlequins)
Replacements:Lee Mears (Bath), Matt Stevens (Saracens), Tom Palmer (Stade Francais), James Haskell (Ricoh Black Rams), Danny Care (Harlequins),Charlie Hodgson (Saracens), Matt Banahan (Bath)
Ireland (vs France, Saurday, kick off 7.45pm)
Rob Kearney (Leinster); Andrew Trimble (Ulster), Keith Earls (Munster), Paddy Wallace (Ulster), Luke Fitzgerald (Leinster); Ronan O'Gara (Munster), Eoin Reddan (Leinster); Cian Healy (Leinster), Rory Best (Ulster), Mike Ross (Leinster), Donncha O'Callaghan (Munster), Leo Cullen (Leinster, captain), Donnacha Ryan (Munster), Sean O'Brien (Leinster), Denis Leamy (Munster)
Replacements: Jerry Flannery (Munster), Tony Buckley (Sale Sharks), Paul O'Connell (Munster), Jamie Heaslip (Leinster), Conor Murray (Munster), Fergus McFadden (Leinster), Felix Jones (Munster)
NB Bold denotes Lions tourist