England head coach Eddie Jones makes just two changes after the 42-39 defeat in the opening Test last weekend with Brad Shields making his first start at blindside flanker and Joe Launchbury coming in for Nick Isiekwe after recovering from a calf injury.
Leicester Tigers scrum-half Youngs makes his 76th England appearance, while Ford moves on to 47 and May to 26 in Bloemfontein.
Kick-off is at 4.05pm UK time and there is live coverage on Sky Sports Action and Main Event.
Head coach Jones said: “We have come here to win the series and the squad is ready to go out and beat them this weekend. We have had a very good preparation this week and the intensity and executions in those sessions are going to put us in a good position for Saturday.
“When you have a win like South Africa did on Saturday, you come into the game with a bit of confidence so we have to make sure we dent the Springboks' confidence early. Bloemfontein is a very fast ground at altitude. It has an average of 60 points per Test match so we are anticipating an ebb-and-flow type game like we had in Johannesburg.”
The final match of the tour is in Cape Town on Saturday, June 23.
England (v South Africa, Saturday)
15 Elliot Daly (Wasps, 19 caps)
14 Jonny May (Leicester Tigers, 35 caps)
13 Henry Slade (Exeter Chiefs, 11 caps)
12 Owen Farrell (Saracens, 59 caps)
11 Mike Brown (Harlequins, 70 caps)
10 George Ford (Leicester Tigers, 46 caps)
9 Ben Youngs (Leicester Tigers, 75 caps)
1 Mako Vunipola (Saracens, 50 caps)
2 Jamie George (Saracens, 26 caps)
3 Kyle Sinckler (Harlequins, 11 caps)
4 Joe Launchbury (Wasps, 52 caps)
5 Maro Itoje (Saracens, 20 caps)
6 Brad Shields (Hurricanes/ Wasps, 1 cap)
7 Tom Curry (Sale Sharks, 2 cap)
8 Billy Vunipola (Saracens, 35 caps)
16 Luke Cowan-Dickie (Exeter Chiefs, 6 caps)
17 Joe Marler (Harlequins, 57 caps)
18 Harry Williams (Exeter Chiefs, 9 caps)
19 Mark Wilson (Newcastle Falcons, 2 caps)
20 Nathan Hughes (Wasps, 15 caps)
21 Ben Spencer (Saracens, 1 cap)
22 Danny Cipriani (Wasps, 14 caps)
23 Denny Solomona (Sale Sharks, 3 caps)