Australia see Wales as an opportunity to take their second place ranking back but they will have to play them without lock Sitaleki Timani who has been suspended.
The Wallabies are currently third in the IRB standings, but assured of a top-four spot ahead of Monday's pool draw for the 2015 World Cup, unlike Wales, who are staring at dropping out of the top eight should they lose.
An Australian victory would see them leapfrog South Africa and playmaker Berrick Barnes said it would be just reward after an injury-ravaged season for the national set-up.
"It would be huge. We started there and to finish there would probably be a great reward for the hard work that a lot of blokes have put in, especially the coaching staff," said the Brisbane-born Barnes, likely to start as full-back.
"We've been like a hotel this year, people have been coming to stay left, right and centre and then leaving.
"The coaching staff, they've adjusted and handled it. It has been a credit to them."
Barnes, who spent his first senior season playing professional rugby league for Brisbane Broncos, will win his 50th cap at the Millennium Stadium on Saturday, a situation that didn't look so likely in early 2011.
At that time, Barnes sustained a series of head injuries that left him suffering "footballer's migraine", a condition that includes a throbbing head, sensitivity to light, nausea and ringing in the ears.
It was serious enough that he sat out most of the Super 15 season in 2011 before he made his comeback in time for the World Cup in New Zealand.
"There's only 37 players that have played 50 Tests in the history of Australian rugby," the gifted 26-year-old Waratahs player said.
"It really is a nice milestone and a good place to do it in Wales here. I've got a lot of fond memories."
Barnes said he would have to put off-pitch friendships to one side when he takes to the paddock.
"I really like the Welsh people they've got a really good grasp of rugby and a great passion for it," he said.
"In particular I get on really well with their boys too. They are a good bunch of lads. It's a bit of a step back to the old school. You rip in on the field and then you have a beer afterwards and a good chin wag and that's how footy should be."
Barnes added: "They're desperate and we've been desperate a number of times this year and have responded well from it and I definitely know how they'd be feeling.
"This is a game where they can mark out a line in the sand before the Six Nations. It's a big opportunity for them. So they've got their reasons and we've got ours."
The Wallabies, who beat Wales to third place in the World Cup and then notched up three straight wins over the Welsh on summer tour, got their autumn series off to a disastrous start with a 33-6 defeat by France.
They have since rebounded with victories over England (20-14) and Italy (22-19), Barnes insisting there would have to be a marked improvement on the second period they played against the Italians, when they let a 22-6 lead slip away.
"I don't think we'll be breathing fire and getting too carried away with it all. I think we've got to play smarter than we did last week," he said.
"The first half was one of the best halves of footy we've played but we didn't play well at all in that second half."
Australia will be without lock forward Sitaleki Timani as he was suspended the player for one week by IRB Judicial Officer, David Martin after he struck a an opponent in the match against Italy.