Middleton makes five changes, two positional, to the side that defeated Italy 7 – 42 at Stadio Mirabello last Sunday.
Charlotte Pearce (Loughborough Lightning) will make her first start for England on the wing, having earned her first international cap last weekend. Danielle Waterman (Wasps FC Ladies) is named at full-back with Ellie Kildunne (Gloucester Hartpury) included at outside centre.
Leanne Riley (Harlequins Ladies) and Katy Daley-Mclean (Darlington Mowden Park Sharks) again start at nine and ten with Rachael Burford (Harlequins Ladies) at inside centre and Abigail Dow (Wasps FC Ladies) - who has scored six tries in three caps - on the wing.
In the scrum Amy Cokayne (Wasps FC Ladies) returns to the front row at hooker alongside Rochelle Clark (Wasps FC Ladies) and Sarah Bern (Gloucester-Hartpury) with Abbie Scott (Harlequins Ladies) and Tamara Taylor (Darlington Mowden Park Sharks) in the second row.
Elsewhere the back row remains unchanged with last weekend’s player of the match Poppy Cleall (Saracens Women) at blindside flanker alongside Saracens team mate Marlie Packer at open side. Captain Sarah Hunter (Loughborough Lightning) - who scored a hat-trick of tries last Sunday - completes the back row at No.8.
Lagi Tuima (Bristol Ladies) returns to the side and is included on the bench alongside Lark Davies (Worcester Valkyries) and Rugby World Cup finalists Vickii Cornborough (Harlequins Ladies), Justine Lucas (Wasps FC Ladies) and Izzy Noel-Smith (Bristol Ladies). Zoe Harrison (Saracens Women), Caity Mattinson (Bristol Ladies) and Rowena Burnfield (Richmond FC) are also named as finishers.
Simon Middleton said "We are expecting a physical encounter against Wales. They play an aggressive brand of defence so there will be a lot of pressure on us when we have the ball.
"They also have a strong and well organised set piece, which we saw last week when they played Scotland, this will be a key area of the game. We have kept a good balance of consistency in selection in the forwards while still exploring different combinations out in the backs."
Middleton added: "As a squad we are really looking forward to returning to the Stoop on Saturday and playing our first home game of the tournament."
England secured a 63-0 win over Wales the last time they met in the 2017 Six Nations at Cardiff Arms Park.
England Women match-day 23 v Wales, Six Nations 2018
15. Danielle Waterman (Wasps FC Ladies, 78 caps)
14. Abigail Dow (Wasps FC Ladies, 3 caps)
13. Ellie Kildunne (Gloucester- Hartpury Women, 4 caps)
12. Rachael Burford (Harlequins Ladies, 76 caps)
11. Charlotte Pearce (Loughborough Lightning, 1 cap)
10. Katy Daley-Mclean (Darlington Mowden Park Sharks, 95 caps)
9. Leanne Riley (Harlequins Ladies, 17 caps)
1. Rochelle Clark (Wasps FC Ladies, 133 caps)
2. Amy Cokayne ( Wasps FC Ladies, 36 caps)
3. Sarah Bern (Gloucester Hartpury, 16 caps)
4. Abbie Scott (Harlequins Ladies, 25 caps)
5. Tamara Taylor (Darlington Mowden Park Sharks, 112 caps)
6. Poppy Cleall (Saracens Women, 18 caps)
7. Marlie Packer (Saracens Women, 55 caps)
8. Sarah Hunter © (Loughborough Lightning, 102 caps)
16. Lark Davis (Worcester Valkyries, 7 caps)
17. Vicky Cornborough (Harlequins Ladies, 34 caps)
18. Justine Lucas (Wasps FC Ladies, 28 caps)
19. Rowena Burnfield (Richmond FC, 42 caps)
20. Izzy Noel-Smith (Bristol Ladies, 38 caps)
21. Caity Mattinson (Bristol Ladies, 3 caps)
22. Zoe Harrison (Saracens Women, 3 caps)
23. Lagi Tuima (Bristol Ladies, 2 caps)
England Women Six Nations 2018 playing schedule:
Italy 7 – 42 England
Tries: Bern, Cleall, Hunter (3), Kildunne, Dow
Cons: Daley- Mclean (2)
England v Wales
Saturday 10 February, KO 12:15pm, Live Sky Sports Action and Sky Sports Mix
Scotland v England
Friday 23 February, KO 19:30, Live Sky Sports Mix and Sky Sports Arena via red button
France v England
Saturday 10 March, KO 20:00 GMT, Live Sky Sports Action and Sky Sports Mix
Stade des Alpes, Grenoble
England v Ireland
Friday 16 March, KO 17:30, Live Sky Sports Action and Sky Sports Mix
Ricoh Arena, Coventry