Manu Tuilagi teams up with Joe Marchant in the centres, while Elliot Daly is back on the left wing, with Jonny May on the right.
Borthwick named his team on Friday and also included veteran prop Dan Cole in the starting team again ahead of Kyle Sinckler. Ellis Genge and Jamie George complete the front row.
"Everyone knows just what an unpredictably dangerous opposition Fiji can be," Borthwick said.
"However, we have shown in the group stages how we can win games and we will be calling on that experience and determination to ensure we carry on our journey."
Ford was man of the match in the first two games when Farrell was suspended but the two playing together did not work well against Samoa when Ford was taken off early in the second half. Borthwick made it clear all week that he absolutely backed his captain, so Ford was the one to pay the price, dropping to the bench.
The more radical selection was that of Smith, a fly-half for Harlequins, to start at full-back. He has looked England's most dangerous player during the tournament.
Freddie Steward was rested for the Chile game after 28 successive tests at full-back. He returned against Samoa and though his defence and aerial skills are unquestioned, he lacks Smith's attacking instincts and was left out of the 23-man matchday squad for Sunday. The absence of Ford also means that Smith can fill the second playmaker role.
"I've always been impressed with Marcus," said Farrell. "How much he wants the ball and wants to make a difference, and from what I've seen, the bigger the game the more he wants it.
"He's played in big games – he's won the Premiership - and what he showed at full-back against Chile and when coming on in the other games is that he wants to make an impact."
Moving Farrell back to fly-half also opened the door to select two specialist centres, both of whom will have a busy afternoon trying to stop Fiji's direct runners.
"You have a great blend there," Borthwick said. "The power, carry and defensive strength that Manu brings and then the incredible outside break and connection with the outside backs in defence that Joe brings.
"The starting back three is also right for us this week. Marcus has really embraced the opportunity and to have players able to play at the highest level in multiple positions is a real strength."
England have won seven of their games against Fiji, the only defeat coming in their last meeting at Twickenham in August.
"That feels a long time ago now," Farrell said. "Obviously we've reviewed and it was helpful to have played them but we feel like we've moved on now."
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Team:
15. Marcus Smith (Harlequins, 28 caps)
14. Jonny May (Gloucester Rugby, 76 caps)
13. Joe Marchant (Stade Francais, 23 caps)
12. Manu Tuilagi (Sale Sharks, 56 caps)
11. Elliot Daly (Saracens, 62 caps)
10. Owen Farrell – captain (Saracens, 109 caps)
9. Alex Mitchell (Northampton Saints, 9 caps)
1. Ellis Genge – vice-captain (Bristol Bears, 55 caps)
2. Jamie George (Saracens, 82 caps)
3. Dan Cole (Leicester Tigers, 104 caps)
4. Maro Itoje (Saracens, 73 caps)
5. Ollie Chessum (Leicester Tigers, 15 caps)
6. Courtney Lawes – vice-captain (Northampton Saints, 103 caps)
7. Tom Curry (Sale Sharks, 47 caps)
8. Ben Earl (Saracens, 22 caps)
Replacements:
16. Theo Dan (Saracens, 6 caps)
17. Joe Marler (Harlequins, 86 caps)
18. Kyle Sinckler (Bristol Bears, 66 caps)
19. George Martin (Leicester Tigers, 7 caps)
20. Billy Vunipola (Saracens, 73 caps)
21. Danny Care (Harlequins, 93 caps)
22. George Ford – vice-captain (Sale Sharks, 89 caps)
23. Ollie Lawrence (Bath Rugby, 18 caps)