James O'Connor will make his debut for the Reds at flyhalf against the Force in Brisbane on Saturday.
That sees Karmichael Hunt shift to fullback, the position in which he trained most of the pre-season in.
But coach Richard Graham said O'Connor and Hunt would 'split' the role on some first phase and attacking situations.
'James has spent the last two weeks training fully with the team and looks settled. He is motivated to help the team around the field and allow the side to find their attacking framework,' Graham added.
In the other change to the Reds XV thrashed 47-3 by the Brumbies, former All Black Adam Thomson will start his first Vodacom Super Rugby match since 2012 at blindside flank.
Reds – 15 Karmichael Hunt, 14 Chris Kuridrani, 13 Chris Feauai-Sautia, 12 Samu Kerevi, 11 Lachie Turner, 10 James O'Connor, 9 Will Genia, 8 Jake Schatz, 7 Liam Gill, 6 Adam Thomson, 5 James Horwill, 4 Marco Kotze, 3 Sam Talakai, 2 Saia Fainga'a, 1 James Slipper (c).
Subs: 16 James Hanson, 17 Ben Daley, 18 Sef Faagase, 19 Tom Murday, 20 Curtis Browning, 21 Nick Frisby, 22 Sam Johnson, 23 Campbell Magnay.
Photo: Bradley Kanaris/Getty Images