Ben Tapuai and Adam Ashley-Cooper will become the Wallabies' eighth centre pairing used in 13 Tests this year when they take on England at Twickenham.
The injury-ravaged Wallabies have used 41 players in 12 Tests and lost regular inside centre Pat McCabe to a neck strain during the week, forcing coach Robbie Deans to reshuffle his backline for Saturday's (Sunday AEDT) clash.
Digby Ioane returns on the wing with Ashley-Cooper pushing to his preferred spot of No.13, leaving Tapuai to move in from outside centre to No.12, a position he plays regularly with Queensland.
Tapuai, 23, will be lining up in just his fifth Test and his first at inside centre for Australia and is marking South African-born No.12 Brad Barritt.
While Ashley-Cooper faces the daunting task of stopping Samoan-born, 110kg giant, Manusamoa Tuilagi.
Ashley-Cooper, who will win his 75th Test cap, played outside Tapuai on the wing in last week's demoralising 33-6 hammering loss to France in Paris.
He feels they will click as a combination in the cauldron of Twickenham where a capacity crowd of 82,000 is expected.
"I think Ben will do a great job. He's played a lot of football there for the Queensland Reds. He's comfortable there and I'm comfortable at 13," Ashley-Cooper said.
"We've had a good training week and we've prepared a lot together this year in the 12 and 13 combination at training ... I feel that we have a good midfield combination.
"Hopefully we can go out there and prove a few critics wrong."
Ashley-Cooper said the defensive assignment wasn't just about stopping the England centres.
"We've really got to have the awareness across the field. First and foremost the job is there to shut them down and hopefully not give them too much gain line," Ashley-Cooper said.
"We need to be aware across the park. Guys like Chris Ashton will be looking to make runs through the middle and we need to be ready for that as well."
Tapuai, who grew up playing inside centre as a schoolboy, says he will be doing everything he can to help take the pressure off No.10 Kurtley Beale.
"I've been working with Kurtley in the past couple of days. When he's confident, it's great for the team and our confidence can rub off onto each other, so I'll be doing everything I can to make his job easier," he said.
"I've played a lot of rugby at inside centre, this is a big step up but I'm looking forward to it and having Adam Ashley-Cooper outside me is going to make my job easier. He's a great communicator."