Moody and Croft take over from Hendre Fourie (Leeds Carnegie) and James Haskell (Stade Francais) in the back row, Cole replaces David Wilson (Bath Rugby) at tight head and Tindall is in for Matt Banahan (Bath Rugby) at outside centre.
Fourie, Wilson and Banahan are on the bench, where Simon Shaw (London Wasps) returns in place of David Attwood (Gloucester Rugby).
Moody will draw level with Neil Back as England's most-capped flanker when he makes his 66th international appearance. Although Joe Worsley is the most experienced back-row forward in the England squad, 15 of his 77 caps have come at No.8.
England are out to end a run of six international defeats against South Africa and were beaten 42-6 at Twickenham in 2008. There are only two survivors from that game in England's starting line-up two years on: Harlequins No.8 Nick Easter and Stade Francais lock Tom Palmer.
15 Ben Foden (Northampton Saints)
14 Chris Ashton (Northampton Saints)
13 Mike Tindall (Gloucester Rugby)
12 Shontayne Hape (Bath Rugby)
11 Mark Cueto (Sale Sharks)
10 Toby Flood (Leicester Tigers)
9 Ben Youngs (Leicester Tigers)
1 Andrew Sheridan (Sale Sharks)
2 Dylan Hartley (Northampton Saints)
3 Dan Cole (Leicester Tigers)
4 Courtney Lawes (Northampton Saints)
5 Tom Palmer (Stade Francais)
6 Tom Croft (Leicester Tigers)
7 Lewis Moody (Bath Rugby, captain)
8 Nick Easter (Harlequins)
16 Steve Thompson (Leeds Carnegie)
17 David Wilson (Bath Rugby)
18 Simon Shaw (London Wasps)
19 Hendre Fourie (Leeds Carnegie)
20 Danny Care (Harlequins)
21 Charlie Hodgson (Sale Sharks)
22 Matt Banahan (Bath Rugby)