Jonny May and Ben Youngs kick of the autumn international period with starting spots for England against South Africa, while Leicester Tigers clubmates George Ford and Manu Tuilagi are among the replacements at Twickenham.
Tuilagi is in line for his first international appearance since the match against Wales in the 2016 Six Nations.
England head coach Eddie Jones includes Dylan Hartley and Owen Farrell as co-captains for the first Test of the Quilter Internationals on Saturday.
George Kruis, Jack Nowell and Ben Te’o are included for the first time since last season’s Six Nations, while Exeter prop Alec Hepburn starts in an England shirt for the first time. Uncapped forwards Zach Mercer and Ben Moon are on the bench.
On England’s preparation ahead of Saturday, Jones said: “We’ve become very well organised in our set-piece and have done a lot of good work in Portugal over the last week. We have put in a new defence system and our attack looks more organised than it was on the South Africa tour.
“Against South Africa you have got the physical battle up front and then you have to be tactically smart in how you attack against them. We need to find ways to gain momentum, then once we find momentum, convert that to points.”
There is live coverage from Twickenham on Sky Sports.
Tigers supporters can watch the game ‘as live’ in the Final Whistle at Welford Road immediately after Saturday’s Premiership Rugby Cup fixture between Leicester Tigers and Worcester Warriors.
England (v South Africa, Saturday 3.00pm)
15 Elliot Daly (Wasps, 21 caps)
14 Jack Nowell (Exeter Chiefs, 26 caps)
13 Henry Slade (Exeter Chiefs, 13 caps)
12 Ben Te’o (Worcester Warriors, 13 caps)
11 Jonny May (Leicester Tigers, 37 caps)
10 Owen Farrell (Saracens, 61 caps) (co-captain)
9 Ben Youngs (Leicester Tigers, 77 caps)
1 Alec Hepburn (Exeter Chiefs, 2 caps)
2 Dylan Hartley (Northampton Saints, 93 caps) (co-captain)
3 Kyle Sinckler (Harlequins, 13 caps)
4 Maro Itoje (Saracens, 22 caps)
5 George Kruis (Saracens, 25 caps)
6 Brad Shields (Wasps, 2 caps)
7 Tom Curry (Sale Sharks, 4 caps)
8 Mark Wilson (Newcastle Falcons, 4 caps)
16 Jamie George (Saracens, 28 caps)
17 Ben Moon (Exeter Chiefs, uncapped)
18 Harry Williams (Exeter Chiefs, 11 caps)
19 Charlie Ewels (Bath Rugby, 6 caps)
20 Zach Mercer (Bath Rugby, uncapped)
21 Danny Care (Harlequins, 81 caps)
22 George Ford (Leicester Tigers, 47 caps)
23 Manu Tuilagi (Leicester Tigers, 26 caps)