Wallabies coach Dave Rennie has confirmed Kurtley Beale will make his starting return at fullback to face England.
Beale comes into fullback with Jordan Petaia (hamstring) ruled out, pushing Andrew Kellaway back to his usual position on the wing.
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Meanwhile, Rennie has been forced to change starting props after regular starters Allan Alaalatoa and Taniela Tupou were ruled out of the Test with concussion symptoms.
James Slipper will make the switch to tighthead, a position he filled in during their loss to Scotland, with Angus Bell elevated to the starting side.
It will mark the first time Slipper has started in the position at the international level since 2012 against New Zealand, having played there for the Brumbies during Super Rugby AU
Alaalatoa and Tupou's unavailability sees Tom Robertson and new Wallaby Ollie Hoskins added to the side, with Hoskins in line to become Wallaby number 949.
"We've got a couple of tighthead outs so Slips has the most experience so he'll go across," Rennie told the media. "Tom Robertson has some experience in the past but we prefer him as a loosehead so it was needed.
"With a six day turnaround (Alaalatoa and Tupou) needed to be right by Monday with no symptoms basically. They woke up fine but as the day progressed, once you get a little bit of a headache they were out.
"We'd planned if we lost one or both, we needed cover so we brought Ollie in."
In further changes on the bench, Tolu Latu will make his return from the bench, joining Hoskins and Robertson.
Latu has not featured for the Wallabies since the 2019 World Cup.
Along with this, Noah Lolesio has been added as the back-up playmaker, with Izaia Perese rounding out the finishers.
“Playing England at a packed Twickenham is one of the toughest assignments in Test Rugby but we're excited by that," Rennie added in a statement.
"While it's disappointing for Taniela and Allan who weren't able to pass their protocols within the six-day turnaround, it's created an opportunity for Ollie to realise a lifelong dream.
"He's impressed us with his dedication and diligence to get up to speed quickly and we're confident he'll do a good job for us."
1. Angus Bell (14 Tests)
2. Folau Fainga’a (23 Tests)
3. James Slipper (112 Tests)
4. Rory Arnold (27 Tests)
5. Izack Rodda (32 Tests)
6. Rob Leota (4 Tests)
7. Michael Hooper (c) (117 Tests)
8. Rob Valetini (16 Tests)
9. Nic White (45 Tests)
10. James O’Connor (59 Tests)
11. Tom Wright (8 Tests)
12. Hunter Paisami (13 Tests)
13. Len Ikitau (11 Tests)
14. Andrew Kellaway (11 Tests)
15. Kurtley Beale (93 Tests)
Replacements
16. Tolu Latu (19 Tests)
17. Tom Robertson (26 Tests)
18. Oliver Hoskins*
19. Will Skelton (19 Tests)
20. Pete Samu (17 Tests)
21. Tate McDermott (13 Tests)
22. Noah Lolesio (8 Tests)
23. Izaia Perese (1 Test)
*denotes uncapped