The Wallabies have named Mike Harris and Christian Leali'ifano in the centres to face Scotland at Murrayfield on Saturday.
Five players are unavailable after being suspended for late-night drinking in Dublin last weekend, including Nick Cummins, Adam Ashley-Cooper, Tatafu Polota-Nau, Benn Robinson and Liam Gill.
Injuries and suspensions have deprived the Wallabies of a number of backline options, including Cummins, Ashley-Cooper, Tevita Kuridrani and Matt Toomua.
As a result Harris fills in for the injured Toomua at inside centre, with Leali'ifano completing his return from injury to partner Harris in midfield. Leali'ifano will also take over the goal-kicking duties from starting fly-half Quade Cooper.
Chris Feauai-Sautia makes his first start on the left wing at just 20 years of age in place of the Cummins, with Joe Tomane returning on the opposite flank for Ashley-Cooper.
Will Genia, Quade Cooper and Israel Folau all remain from the 32-15 win over Ireland last weekend.
The Wallabies forward pack remains unchanged from Dublin, with Ben Mowen continuing to captain the side from number eight.
Saia Fainga'a and Ben Alexander are added to the replacements along with Ben McCalman, with Nick Phipps and Bernard Foley the two other options in the backs alongside scrum-half Nic White.
Australia: 15 Israel Folau, 14 Joe Tomane, 13 Christian Leali'ifano, 12 Mike Harris, 11 Chris Feauai-Sautia, 10 Quade Cooper, 9 Will Genia, 8 Ben Mowen (capt), 7 Michael Hooper, 6 Scott Fardy, 5 James Horwill, 4 Rob Simmons, 3 Sekope Kepu, 2 Stephen Moore, 1 James Slipper.
Replacements: 16 Saia Fainga'a, 17 Ben Alexander, 18 Paddy Ryan, 19 Sitaleki Timani, 20 Ben McCalman, 21 Nic White, 22 Nick Phipps, 23 Bernard Foley.
Date: Saturday, November 23
Venue: Murrayfield, Edinburgh
Kick-off: 18:00 GMT
Referee: Jaco Peyper (South Africa)
Assistant referees: Pascal Gauzčre (France), Francisco Pastrana (Argentina)
Television match official: Geoff Warren (England) Lyndon Bray (SANZAR)