Tigers Academy graduate Martin, 19, only made his Premiership debut in the restart phase of last season and has made seven first-team appearances before being added to the England squad as injury cover last week.
He is named on the bench by national coach Eddie Jones for the Guinness Six Nations match in Cardiff.
Ford and Youngs are together at half-back with prop Genge among the replacements.
Elliot Daly is set to make his 50th appearance for England in a team captained by Owen Farrell, while Jamie George returns at hooker.
Jones said: “Wales is a really special fixture and rivalry. There is a long history between the two nations and the game means a lot to both countries.
“We know we’ll be up against a strong Welsh challenge on Saturday, but we’ve worked really hard in training this week and have got a very good team to face it.
“We want to show people what we are capable of, keep building our performances and the best is yet to come from this England team.”
Wales versus England is live on BBC One and BBC Radio 5 Live. Kick-off at the Principality Stadium is at 4.45pm.
15 Elliot Daly (Saracens, 49 caps)
14 Anthony Watson (Bath Rugby, 48 caps)
13 Henry Slade (Exeter Chiefs, 36 caps)
12 Owen Farrell (Saracens, 90 caps)(c)
11 Jonny May (Gloucester Rugby, 63 caps)
10 George Ford (Leicester Tigers, 74 caps)
9 Ben Youngs (Leicester Tigers, 106 caps)
1 Mako Vunipola (Saracens, 64 caps)
2 Jamie George (Saracens, 56 caps)
3 Kyle Sinckler (Bristol Bears, 41 caps)
4 Maro Itoje (Saracens, 45 caps)
5 Jonny Hill (Exeter Chiefs, 6 caps)
6 Mark Wilson (Newcastle Falcons, 20 caps)
7 Tom Curry (Sale Sharks, 30 caps)
8 Billy Vunipola (Saracens, 58 caps)
16 Luke Cowan-Dickie (Exeter Chiefs, 28 caps)
17 Ellis Genge (Leicester Tigers, 25 caps)
18 Will Stuart (Bath Rugby, 10 caps)
19 Charlie Ewels (Bath Rugby, 18 caps)
20 George Martin (Leicester Tigers, uncapped)
21 Ben Earl (Bristol Bears, 10 caps)
22 Dan Robson (Wasps, 9 caps)
23 Max Malins (Bristol Bears, 5 caps)