Shannon Frizell and Sio Tomkinson come in at blindside flanker and right wing respectively, while Jesse Parete replaces the injured Paripari Parkinson.
Frizell and Tomkinson will step for Dillon Hunt, who drops to the bench, and Tima Fainga'anuku.
James Lentjes will lead the side, which is also sticking with the 10-12 combination of Mitch Hunt and Josh Ioane.
Counties-Manukau Irish prop, Conan O’Donnell gets an opportunity after coming in for the injured Jeff Thwaites.
The match kicks off at 9.15pm (NZ time) in Canberra.
Highlanders team to play the Brumbies
Josh McKay, Sio Tomkinson, Rob Thompson, Josh Ioane, Jona Nareki, Mitch Hunt, Aaron Smith, Marino Mikaele-Tu'u, James Lentjes (c), Shannon Frizell, Josh Dickson, Jesse Parete, Siate Tokolahi, Liam Coltman, Ayden Johnstone. Reserves: Ash Dixon, Daniel Lienert-Brown, Conan O'Donnell, Jack Whetton, Dillon Hunt, Kayne Hammington, Michael Collins, Teariki Ben-Nicholas.