The series, which opens with the first Test in Brisbane on Saturday, pits the Six Nations champions against the Tri-Nations winners and also provides something of an appetiser for next year's British and Irish Lions tour Down Under.
Wales have not taken a major scalp in the southern hemisphere since beating Australia at the 1987 World Cup, however, and the Wallabies won both encounters at the back end of last season, including the World Cup third place play-off.
Since then, though, the young Welsh team have secured a Grand Slam in the Six Nations and are bursting with confidence they can reproduce the sort of fearless displays that took them to the World Cup semi-finals last year.
"The history books are against us... but the thing about these guys is they are very young... and they want to make their own history," Wales defensive coach Shaun Edwards said.
"The thing that rankles them is they've never beaten Australia and that will be a big driving force for them, to rectify that in Australia."
Australia have high standards and their own semi-final departure at the World Cup at the hands of the All Blacks was considered something of a failure.
Injury means they will be without the "Three Amigos" of talented backs Kurtley Beale, James O'Connor and Quade Cooper as well as lock and skipper James Horwill for the series, which also includes tests in Melbourne and Sydney.
They also crashed to a shock 9-6 defeat at the hands of Scotland in their opening match of the year on Tuesday, a fixture just three days after the final round of Super Rugby that has disrupted their preparations for the Welsh.
Coach Robbie Deans will take some solace from the fact that Australia rebounded from a similar upset at the hands of Samoa last year and scrum-half Will Genia promised a marked improvement at Lang Park on Saturday.
"It won't be good enough, we need to go away and take a hard look at ourselves," he said. "Hopefully we'll get a chance to play rugby in better conditions but it's a learning experience and a very tough one at that.
"(But) there's no fear, it's another Test match. It's a new game. We'll learn what we need to learn from this experience and we'll move on. The last time we had a result like this against Samoa, good things came from it..."
Genia's contest against Wales scrum-half Mike Phillips will be one of several intriguing personal battles in the series - the little Australian general against the hulking Welshman who plays like a fourth loose forward.
After failing to follow through on the Grand Slams of 2005 and 2008, Phillips said the Welsh were determined to ensure this year's feat formed the foundation of a move back into the top echelons of Test rugby for the principality.
"It's all about winning and we want to carry on in that way and move to the next level," he said. "We want to push on and get the next big scalp."
Skipper Sam Warburton will be back after three months on the sidelines to go head-to-head in another fascinating duel with Australian openside flanker David Pocock, who skippered the Wallabies against Scotland.
The Australian pack's increasing confidence that they can take on anyone in the world in the tight should be sorely tested by the Welsh, while the visitors' hulking backline will be another challenge.
Australia showed they have few peers defensively with a incredible performance against South Africa in the World Cup quarter-finals and their main concern, unusually, might be about where their offensive spark might come from.
With their first four fly-half choices unavailable, Deans has been reduced to choosing between Berrick Barnes, who has been struggling for form, and the inexperienced Mike Harris, a solid if unspectacular playmaker.
Edwards, who will be working under Rob Howley on the tour in the continued absence of the injured head coach Warren Gatland, warned, however, that the hosts should never be underestimated.
"Every time you play against Australia, you are playing against a very good team, whoever puts on that green and gold jersey is going to be a very good player," Edwards said.