Owen Farrell will start at fly-half in a reshuffled England line-up to face South Africa at Twickenham on Saturday. England coach Eddie Jones has handed Farrell the sole control of the backline with Ford relegated to the bench.
Manu Tuilagi is set to feature in a Test for the first time since 2016 when he comes off the bench.
Sale Sharks winger Chris Ashton has lost out to Jack Nowell as he failed to find a place in the 23.
Jones has also recalled the fit-again Ben Te’o in midfield alongside Henry Slade despite the Worcester centre having played just 28 minutes for his club this season.
“Against South Africa you have got the physical battle up front and then you have to be tactically smart in how you attack against them. We need to find ways to gain momentum, then once we find momentum, convert that to points,” said Jones.
“We’ve become very well organised in our set piece and have done a lot of good work in Portugal over the last week.
"We have put in a new defence system and our attack looks more organised than it was on the South Africa tour.”
England starting XV
15 Elliot Daly (Wasps, 21 caps)
14 Jack Nowell (Exeter Chiefs, 26 caps)
13 Henry Slade (Exeter Chiefs, 13 caps)
12 Ben Te’o (Worcester Warriors, 13 caps)
11 Jonny May (Leicester Tigers, 37 caps)
10 Owen Farrell (Saracens, 61 caps) co-captain
9 Ben Youngs (Leicester Tigers, 77 caps)
1 Alec Hepburn (Exeter Chiefs, 2 caps)
2 Dylan Hartley (Northampton Saints, 93 caps) co-captain
3 Kyle Sinckler (Harlequins, 13 caps)
4 Maro Itoje (Saracens, 22 caps)
5 George Kruis (Saracens, 25 caps)
6 Brad Shields (Wasps, 2 caps)
7 Tom Curry (Sale Sharks, 4 caps)
8 Mark Wilson (Newcastle Falcons, 4 caps)
16 Jamie George (Saracens, 28 caps)
17 Ben Moon (Exeter Chiefs, uncapped)
18 Harry Williams (Exeter Chiefs, 11 caps)
19 Charlie Ewels (Bath Rugby, 6 caps)
20 Zach Mercer (Bath Rugby, uncapped)
21 Danny Care (Harlequins, 81 caps)
22 George Ford (Leicester Tigers, 47 caps)
23 Manu Tuilagi (Leicester Tigers, 26 caps)