The Australia international has been sidelined for the past two weeks with a knee injury, however Ioane has been declared fit to return.
Ioane comes into the side for the benched Dom Shipperley, with Rod Davies retaining his place after he double against the Chiefs.
The only other change among the replacements sees Saia Faingaa provide cover at hooker.
The Brumbies, who have a two-point lead over the Reds in the standings, welcome back Fotu Auelua and Tevita Kuridrani.
Auelua comes into the back row at No 8, with Ben Mowen moving to blindside and Jordan Smiler dropping to the bench.
With Andrew Smith sidelined with a hamstring injury, Kuridrani takes over at outside centre. Clyde Rathbone will provide cover from the bench.
Reds: 15 Jono Lance, 14 Rod Davies, 13 Anthony Faingaa, 12 Ben Tapuai, 11 Digby Ioane, 10 Quade Cooper, 9 Will Genia, 1 Greg Holmes, 2 James Hanson, 3 James Slipper, 4 Rob Simmons, 5 James Horwill (c), 6 Eddie Quirk, 7 Liam Gill, 8 Jake Schatz.
Replacements: 16 Saia Faingaa, 17 Ben Daley, 18 Ed O'Donoghue, 19 Jarrad Butler, 20 Ben Lucas, 21 Chris Feauai-Sautia, 22 Dom Shipperley.
Brumbies: 15 Jesse Mogg, 14 Henry Speight, 13 Tevita Kuridani, 12 Christian Lealiifano, 11 Joe Tomane, 10 Matt Toomua, 9 Nic White, 1 Ben Alexander, 2 Stephen Moore, 3 Dan Palmer, 4 Peter Kimlin, 5 Sam Carter, 6 Ben Mowen, 7 George Smith, 8 Fotu Auelua.
Replacements: 16 Siliva Siliva, 17 Scott Sio, 18 Jordan Smiler, 19 Colby Faingaa, 20 Ian Prior, 21 Pat McCabe, 22 Clyde Rathbone.