Farrell, 31, will start on the bench, with prop forward Ellis Genge named by coach Steve Borthwick as captain for the Twickenham clash against the reigning Six Nations champions.
"The players selected to face our visitors are again a reflection of what I see to be the right balance of personnel for the challenge we face in this game," said Borthwick.
"Marcus Smith starts at fly-half and Dave Ribbans returns to the match-day 23. Congratulations to Ellis Genge, who will captain the side for the first time."
Smith started at fly-half, with Farrell at inside centre, for Borthwick's first game in charge, a tournament-opening 29-23 defeat by Scotland at Twickenham last month.
But he then restored Farrell to the No 10 shirt for the subsequent wins over Italy and Wales.
The 24-year-old Smith was released to play for club side Harlequins against Exeter last weekend and he responded with a fine attacking display while landing five out of six goal kicks.
The once-reliable Farrell has enjoyed a meagre 47 percent success rate off the tee in the opening three rounds of the Six Nations.
England's 20-10 win away to Wales would have been more emphatic had Farrell not missed four out of six shots at goal.
England team:
15. Freddie Steward, 14. Max Malins, 13. Henry Slade, 12. Ollie Lawrence, 11. Anthony Watson, 10. Marcus Smith, 9. Jack van Poortvliet; 8. Alex Dombrandt, 7. Jack Willis, 6. Lewis Ludlam, 5. Ollie Chessum, 4. Maro Itoje, 3. Kyle Sinckler, 2. Jamie George 1. Ellis Genge
Replacements: 16. Jack Walker, 17. Mako Vunipola, 18. Dan Cole 19. David Ribbans, 20. Ben Curry, 21. Alex Mitchell, 22. Owen Farrell, 23. Henry Arundell
