The Saints duo are joined in the starting XV by Sam Burgess, Owen Farrell and Billy Vunipola, with Jonathan Joseph, George Ford and Ben Morgan dropping out.
A third Saint. Kieran Brookes, is among the replacements once more on Saturday evening, where Alex Goode is also a new face due to Joseph's Injury.
Head coach Stuart Lancaster is hoping home advantage pays on a huge evening.
"We have a lot of respect for the Wales coaching team and their players," Lancaster said. "They are a high quality side and I am sure it will be some occasion on Saturday evening.
"The support at Twickenham last week was incredible with the crowd really getting behind us and we will need them again this week to lift the players against a tough Wales team."
England versus Wales is an 8pm kick off, live on ITV.
ENGLAND TEAM TO PLAY WALES
Rugby World Cup 2015
Saturday, September 26th, 2015
Kick off 8pm
15 Mike Brown (Harlequins, 40 caps)
14 Anthony Watson (Bath Rugby, 12 caps)
13 Brad Barritt (Saracens, 24 caps)
12 Sam Burgess (Bath Rugby, 3 caps)
11 Jonny May (Gloucester Rugby, 17 caps)
10 Owen Farrell (Saracens, 32 caps)
9 Ben Youngs (Leicester Tigers, 50 caps)
1 Joe Marler (Harlequins, 34 caps)
2 Tom Youngs (Leicester Tigers, 25 caps)
3 Dan Cole (Leicester Tigers, 53 caps)
4 Geoff Parling (Exeter Chiefs, 26 caps)
5 Courtney Lawes (Northampton Saints, 41 caps)
6 Tom Wood (Northampton Saints, 39 caps)
7 Chris Robshaw (capt)(Harlequins, 40 caps)
8 Billy Vunipola (Saracens, 20 caps)
16 Rob Webber (Bath Rugby, 14 caps)
17 Mako Vunipola (Saracens, 24 caps)
18 Kieran Brookes (Northampton Saints, 13 caps)
20 James Haskell (Wasps, 60 caps)
21 Richard Wigglesworth (Saracens, 24 caps)
22 George Ford (Bath Rugby, 14 caps)
23 Alex Goode (Saracens, 18 caps)