England will face the feared South African pack with a depleted front row after Bevan Rodd and Jamie Blamire were given starts in Saturday's climax to the autumn against South Africa.
Injury and an outbreak of coronavirus mean that loosehead prop Rodd will win his second cap while Blamire, who has made only three starts for his club Newcastle, takes the hooking duties.
Joe Marler leaves self-isolation on Friday and so is confined to a bench role for the rematch of the 2019 World Cup final.
Eddie Jones has thrown a curveball on the right wing where outside centre Joe Marchant is picked ahead of specialist Adam Radwan and Max Malins, who has been in free-scoring form for Saracens this season.
Marchant was left out of the original squad for the autumn but a campaign-ending knee injury sustained by Anthony Watson offered a reprieve that culminates in an opportunity against the world champions.
Owen Farrell has been ruled out of the final match of a series that has featured wins over Tonga and Australia by an ankle problem, which will require surgery and 10-12 weeks out, so Marcus Smith forms the midfield alongside Manu Tuilagi and Henry Slade.
Courtney Lawes leads the team for the second time in Farrell’s absence.
"This is our biggest game of the season and the final game of the autumn campaign and we want to finish with a bang," Jones said. "We’ve been really pleased with the preparation this week and how the team has continued to develop over the past month.
"Now we want to put on our best performance this autumn in front of a capacity 82,000 crowd at Twickenham."
England: Freddie Steward; Joe Marchant, Henry Slade, Manu Tuilagi, Jonny May; Marcus Smith, Ben Youngs; Bevan Rodd, Jamie Blamire, Kyle Sinckler; Maro Itoje, Jonny Hill; Courtney Lawes (capt), Sam Underhill, Tom Curry.
Replacements: Nic Dolly, Joe Marler, Will Stuart, Charlie Ewels, Sam Simmonds, Alex Dombrandt, Raffi Quirke, Max Malins.
🗨️ Australia will want to finish their tour on a high note as we'd like to finish our campaign on a high note…..— Welsh Rugby Union 🏉 (@WelshRugbyUnion) November 18, 2021
Wayne Pivac on the Autumn Nations Series finale after naming side to face @wallabies
FULL STORY ➡️ https://t.co/Yx03oEGgWm pic.twitter.com/hrtBDGjYPy
Wing Josh Adams and number eight Aaron Wainwright have recovered from injuries and will start Wales' Autumn Nations Series finale against Australia on Saturday.
Adams was withdrawn just before kick-off when Wales faced Fiji last Sunday due to a calf muscle issue, while Wainwright missed that game because of a shoulder problem.
Elsewhere, prop Tomas Francis has successfully completed concussion return-to-play protocols and is recalled, and Seb Davies takes over from lock Will Rowlands, who suffered a head knock against Fiji.
Other starters include centre Uilisi Halaholo – his first of the autumn – with Halaholo, who tested positive for coronavirus last month and spent 10 days isolating, partnering Nick Tompkins in midfield.
Scarlets’ 93 times-capped centre Jonathan Davies does not feature, with flanker Ellis Jenkins continuing as captain at the Principality Stadium.
Jenkins is joined in the back-row by Wainwright and Taine Basham, and there is a recall for British and Irish Lions prop Wyn Jones, who packs down alongside Ryan Elias and Francis.
Elias, Basham and lock Adam Beard, meanwhile, are the only three players selected to start all of Wales’ autumn games against New Zealand, South Africa, Fiji and Australia.
Wales are seeking a third successive victory over Australia, which includes a pool stage win at the 2019 World Cup, following a run of 13 defeats against the Wallabies.
Wales head coach Wayne Pivac said: "It has been a tough campaign, but one where we have exposed more players to this level of rugby, which all bodes well for the future.
"With the injuries we’ve faced, we have had to adapt, and those are opportunities that some of the players have taken very well.
"Australia have been on the road for a while now – the series they had down south, and a couple of losses in the last couple of games.
"They will be hurting from that and they will want to finish their tour on a high note, as we would like to finish our campaign on a high note. It bodes well for a pretty interesting fixture.
"Dave Rennie (Australia head coach) brings a physical approach to the game, and we certainly expect that from the Australians, but we have to be able to match that and impose ourselves on the game."
🏴 Introducing your Scotland team to play @JRFURugby in this Saturday's Autumn Nations Series match at @BTMurrayfield.— Scottish Rugby (@Scotlandteam) November 18, 2021
Read more ➡️ https://t.co/MOZY3x5mm0#AsOne | @autumnnations pic.twitter.com/zsQPafWYIC
Gregor Townsend has made seven changes to his Scotland side for Saturday's fourth and final Autumn Test against Japan at Murrayfield.
Rufus McLean, Matt Scott, Pierre Schoeman, Matt Fagerson, Nick Haining, Sam Skinner and Stuart McInally all drop out of the XV that started last weekend's 30-15 defeat by South Africa.
Jamie Bhatti, Scott Cummings, Hamish Watson, Josh Bayliss, Darcy Graham, Sam Johnson and George Turner are all added to the team as the Scots bid to round off an encouraging calendar year with a victory.
Glasgow prop Bhatti will make his first Scotland start since the warm-up match against France prior to the 2019 World Cup. His club-mate Bayliss, who made his debut as a replacement against Australia, is handed his first start for the national team at number eight.
Warriors lock Cummings makes his first international appearance of the season after injury, while hooker Turner is back after recovering from the injury he suffered against the Wallabies.
There is the possibility of debuts for two players named in the replacements, with Scarlets prop Javan Sebastian and Sharks back-row forward Dylan Richardson both in the matchday 23 for the first time.