Both sides head into the encounter on the back of three-match losing streaks and looking to regain some momentum ahead of next year's World Cup in France.
Next year's Rugby World Cup will mark 20 years since these two sides competed in the final of the competition, when Jonny Wilkinson memorably won the William Webb Ellis Trophy for England against Eddie Jones's Australia with an extra-time drop-goal.
Right now, though, the prospect of lifting that trophy again next year seems about as far away for both teams as at any other point in the intervening years.
Now ranked sixth and fifth in the world respectively, Australia and England have each lost their last three games, with the latter suffering a particularly chastening 52-21 mauling at the hands of Barbarians in June.
That result piled more pressure on the shoulders of head coach Eddie Jones, whose star has fallen significantly in recent years courtesy of back-to-back Six Nations campaigns in which they have lost more games than they have won.
A third-placed finish in this season's competition flattered them a little, ending with defeats at the hands of Ireland and France in March ahead of the Barbarians humiliation.
Victory on Saturday, and in the three-match series against his home nation, will certainly help to take some of the spotlight off Jones, although serious questions do remain over the direction in which England are heading under the Aussie.
For Australia, Saturday's match represents their first outing of the calendar year, having not yet had a chance to respond from their hugely disappointing end to 2021.
The Wallabies were beaten by Scotland, England and Wales in succession in their final three fixtures of last year, meaning that they have not won a match since their 32-23 triumph over Japan more than eight months ago.
In total, Australia lost seven times in 2021, although they did beat current world champions and number one ranked team South Africa twice in the Rugby Championship.
Nonetheless, head coach Dave Rennie will be desperate to get back to winning ways as quickly as possible and re-establish themselves as contenders for the World Cup next year.
To do so, they will need to start with a rare victory over England in order to regain the Ella-Mobbs Trophy - formerly known as the Cook Cup - for the first time since 2016.
England starting lineup:
Freddie Steward; Jack Nowell, Joe Marchant, Owen Farrell, Joe Cokanasiga; Marcus Smith, Danny Care; Ellis Genge, Jamie George, Will Stuart, Maro Itoje, Jonny Hill, Courtney Lawes (captain), Tom Curry, Billy Vunipola
Replacements: Luke Cowan-Dickie, Mako Vunipola, Joe Heyes, Ollie Chessum, Lewis Ludlam, Jack van Poortvliet, Guy Porter, Henry Arundell.
Australia starting lineup:
Tom Banks; Andrew Kellaway, Len Ikitau, Samu Kerevi, Marika Koroibete; Quade Cooper, Nic White; Angus Bell, David Porecki, Allan Alaalatoa, Darcy Swain, Cadeyrn Neville, Rob Leota, Michael Hooper, Rob Valentini
Head To Head
England have dominated this fixture in recent years, winning all eight meetings between the two old rivals since Jones took charge after the 2015 Rugby World Cup.
That run includes a 3-0 series whitewash on their last visit to Australia in 2016, while their last meeting saw England run out 32-15 winners at Twickenham.
Overall, these two sides have faced off 52 times, with England marginally leading the head to head 26-25, with one draw.
We say: Australia 19-24 England
This is a difficult one to call considering Australia have not been in action yet this year, and considering the form England have been in recently.
It is hard to back the tourists based on that form, but they seem to have the edge over Australia under Jones and will surely produce a much-improved performance compared to the Barbarians defeat.