Freeman has been in the training squad throughout November and finally gets his chance to add to his two caps in place of Jack Nowell, who is named among the replacements.
Coles, who made his debut as lock against Argentina three weeks ago, is in for Sam Simmonds, who also moves to the bench.
In two other pack changes prop Mako Vunipola and hooker Jamie George move to the starting team, swapping places with replacements Ellis Genge and Luke Cowan-Dickie.
England will be desperate to end their November series with a win after their fightback draw against New Zealand, a convincing victory over Japan and an opening defeat by Argentina.
"This is our last game of the autumn and our chance to continue building on the improvements we have made throughout the matches," Jones said.
"We have made steady progress from game-to-game, culminating in a pulsating draw against New Zealand. Now we have the chance to test ourselves against the might of the world champions.
"We’re going out there to light the crowd up. The support at Twickenham was outstanding last week and we want to work hard on the pitch to make sure we have another atmosphere like that again on Saturday."
South Africa named their team earlier in the week and were forced into a series of changes after their English and French-based players were forced to rejoin their clubs because Saturday's game falls outside the international test window.
The Rugby Football Union has an arrangement with the Premiership clubs to allow player release. Last year England edged the Twickenham fixture with South Africa by a point, one of three wins in their last four meetings - the defeat being in the 2019 World Cup final.
England team to face South Africa
15. Freddie Steward (Leicester Tigers, 16 caps)14. Tommy Freeman (Northampton Saints, 2 caps)13. Manu Tuilagi (Sale Sharks, 49 caps)12. Owen Farrell (C) (Saracens, 100 caps)11. Jonny May (Gloucester Rugby, 71 caps)10. Marcus Smith (Harlequins, 16 caps)9. Jack van Poortvliet (Leicester Tigers, 6 caps)1. Mako Vunipola (Saracens, 73 caps)2. Jamie George (Saracens, 71 caps)3. Kyle Sinckler (Bristol Bears, 55 caps)4. Maro Itoje (Saracens, 61 caps)5. Jonny Hill (Sale Sharks, 18 caps)6. Alex Coles (Northampton Saints, 2 caps)7. Tom Curry (Sale Sharks, 44 caps)8. Billy Vunipola (Saracens, 67 caps) Replacements
16. Luke Cowan-Dickie (Exeter Chiefs, 40 caps)17. Ellis Genge (Bristol Bears, 42 caps)18. Will Stuart (Bath Rugby, 24 caps)19. David Ribbans (Northampton Saints, 2 caps)20. Sam Simmonds (Exeter Chiefs, 17 caps)21. Ben Youngs (Leicester Tigers, 120 caps)22. Henry Slade (Exeter Chiefs, 51 caps)23. Jack Nowell (Exeter Chiefs, 44 caps)
