Daly takes centre stage against Boks
England head coach Eddie Jones has named an experienced starting XV with England captain Dylan Hartley leading out a side with a total of 596 international caps between them as they aim to defeat the Springboks for the first time since 2006.
With outside centre Jonathan Joseph carrying a slight groin injury Daly (Wasps) will make his sixth international appearance having come off the bench to earn his previous caps.
In the absence of James Haskell, Tom Wood (Northampton Saints) returns to the England team at flank with Jonny May (Gloucester) also back on the left wing following a lengthy injury lay-off.
Debutants Kyle Sinckler (Harlequins) and Nathan Hughes (Wasps) are named as replacements as is uncapped centre Ben Te'o (Worcester Warriors).
Elsewhere lock Courtney Lawes (Northampton Saints) will earn his 50th England cap on Saturday having made his debut against Australia at Twickenham in 2009. He partners Joe Launchbury in the absence of injured Saracens duo George Kruis and Maro Itoje.
There are also returns for Joe Marler (Harlequins) and Dave Attwood (Bath) who are both among the replacements.
"We’'e picked a matchday 23 with a blend of experience and youth," said Jones.
"We've trained well this week and I am pleased with how the players have come together and responded to some of the things we've asked them to do. The boys are focussed and ready to go.
"We’re looking forward to the game. It's a fantastic opportunity to show how much depth we have in English rugby. With a few influential players not available for selection this is a great opportunity for some of the new faces to put both feet forward and we're backing them to do the job for us.
"Test matches are always about the contest up front and South Africa pride themselves in the set piece but we'll be ready for the challenge."
England also face Fiji, Argentina and Australia in the series and Jones added: "We can’t wait to get back to Twickenham.
"It's a very special stadium and we hope the crowd really gets behind us on Saturday. We want to make Twickenham an intimidating place for opposition teams to play rugby and the fans can contribute to that."
England: 15 Mike Brown, 14 Marland Yarde, 13 Elliot Daly, 12 Owen Farrell, 11 Jonny May, 10 George Ford, 9 Ben Youngs, 8 Billy Vunipola, 7 Tom Wood, 6 Chris Robshaw, 5 Courtney Lawes, 4 Joe Launchbury, 3 Dan Cole, 2 Dylan Hartley (captain), 1 Mako Vunipola.
Replacements: 16 Jamie George, 17. Joe Marler, 18. Kyle Sinckler, 19. Dave Attwood, 20. Nathan Hughes, 21. Danny Care, 22. Ben Te'o, 23 Jonathan Joseph.
Date: Saturday, November 12
Venue: Twickenham Stadium, London
Kick-off: 14.30 (14.30 GMT; 16.30 SA Time)
Referee: Jérôme Garcès (France)
Assistant referees: Glen Jackson (New Zealand), Andrew Brace (Ireland)
TMO: Jon Mason (Wales)
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