Genia will become the tenth Australian Test centurion, almost 10 years on from his debut against New Zealand in 2009.
The 30-year old is one of five changes to Michael Cheika’s side that defeated Italy 26-7 in Padova last weekend.
Fellow centurion Sekope Kepu returns to the starting side at tighthead prop with Tolu Latu to start at hooker after sitting out last weekend’s clash.
Jack Maddocks will earn just his third Test start with Dane Haylett-Petty on the right wing to allow Israel Folau to remain at fullback.
Cheika has also confirmed a six-two split on the bench with overcast conditions forecast for Saturday afternoon in London.
The Wallabies will wear their Indigenous jersey for just the second time when they run out at Twickenham, after earning a hard-fought 23-18 win over New Zealand in the jersey’s debut last year.
Australia have only won twice in their past 10 meetings against the Old Enemy with the last Wallabies victory back in 2015 at the Rugby World Cup when England were the first hosts to be eliminated in the pool stage.
Qantas Wallabies team to play England at Twickenham Stadium, London on Saturday 24 November, 3.00pm local (2.00am AEDT)
1. Scott Sio (54 Tests)
2. Tolu Latu (11 Tests)
3. Sekope Kepu (102 Tests)
4. Izack Rodda (16 Tests)
5. Adam Coleman (30 Tests)
6. Jack Dempsey (9 Tests)
7. Michael Hooper (c) (90 Tests)
8. David Pocock (77 Tests)
9. Will Genia (99 Tests)
10. Matt To’omua (41 Tests)
11. Jack Maddocks (6 Tests)
12. Bernard Foley (67 Tests)
13. Samu Kerevi (24 Tests)
14. Dane Haylett-Petty (30 Tests)
15. Israel Folau (72 Tests)
16. Tatafu Polota-Nau (88 Tests)
17. Jermaine Ainsley (2 Tests)
18. Allan Alaalatoa (30 Tests)
19. Rob Simmons (93 Tests)
20. Ned Hanigan (19 Tests)
21. Pete Samu (8 Tests)
22. Nick Phipps (70 Tests)
23. Sefa Naivalu (9 Tests)
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