“This is an opportunity for us to finish the tournament with a strong performance against Uruguay and a chance for the likes of young players such as Jack Nowell and Henry Slade to play in a World Cup,” said England head coach Stuart Lancaster.
“We owe it to ourselves and the supporters who have been brilliant throughout. This is an important game for rugby in the north of England and we want to give those people who have been looking forward to this game something to cheer about.”
Slade and Nowell will be joined in the England team by scrum-half Danny Care (Harlequins) and full-back Alex Goode (Saracens), also making their RWC bows.
In the pack, Mako Vunipola (Saracens) starts in place of Joe Marler (Harlequins) while James Haskell (Wasps) and Nick Easter (Harlequins) replace Tom Wood (Northampton Saints) and Ben Morgan (Gloucester Rugby).
Lancaster said: “Brad Barritt (arm) and Courtney Lawes (knee) are not available this weekend and Ben Morgan (dead leg) and Ben Youngs (ankle) will not be able to train fully until Thursday.
England (v Uruguay, City of Manchester Stadium, 8pm, BST, Saturday, October 10, 2015)
15 Alex Goode (Saracens, 18 caps)
14 Anthony Watson (Bath Rugby, 14 caps)
13 Henry Slade (Exeter Chiefs, 1 cap)
12 Owen Farrell (Saracens, 34 caps)
11 Jack Nowell (Exeter Chiefs, 9 caps)
10 George Ford (Bath Rugby, 16 caps)
9 Danny Care (Harlequins, 52 caps)
1 Mako Vunipola (Saracens, 26 caps)
2 Tom Youngs (Leicester Tigers, 27 caps)
3 Dan Cole (Leicester Tigers, 55 caps)
4 Joe Launchbury (Wasps, 27 caps)
5 Geoff Parling (Exeter Chiefs, 28 caps)
6 James Haskell (Wasps, 61 caps)
7 Chris Robshaw (capt, Harlequins, 42 caps)
8 Nick Easter (Harlequins, 53 caps)
16 Jamie George (Saracens, 2 caps)
17 Joe Marler (Harlequins, 36 caps)
18 David Wilson (Bath Rugby, 43 caps )
19 George Kruis (Saracens, 9 caps)
20 Tom Wood (Northampton Saints, 41 caps)
21 Richard Wigglesworth (Saracens, 26 caps)
22 Jonathan Joseph (Bath Rugby, 15 caps)
23 Mike Brown (Harlequins, 42 caps)