Dylan Hartley and Tom Wood will be on the bench for England’s game against Samoa on Saturday.
The pair had started the previous two autumn Tests, against New Zealand and South Africa, but will only be among the replacements at Twickenham this weekend.
Bath’s Rob Webber takes Hartley’s place in the side, while Wood is replaced by Wasps flanker James Haskell.
Courtney Lawes is the solitary Saints presence in a starting 15 that includes both George Ford and Owen Farrell, who shifts from 10 to 12.
England will be bidding to claim their first victory of the autumn, having suffered narrow defeats to the All Blacks and the Springboks.
“Those selected have a great opportunity to show what they can do against what will be a highly motivated Samoa team,” said England head coach Stuart Lancaster.
“It’s great to give George (Ford) a start in this series, having missed the summer tour through injury. He has been impressive in camp and now fully up to speed with the game plan and he is ready to run the game.
“Owen (Farrell) switches to 12 and I am sure will support George well. In the back row both James (Haskell) and Ben (Morgan) have been in great form and I am sure they will bring their physical presence to the game.
“Hooker is another competitive position and we believe Rob (Webber) is ready for the start and will continue the progress he made on the New Zealand tour.”