Ioane will make his return from a five-week suspension at Eden Park as one of three changes to the starting side which fell 23-13 to the Stormers in Brisbane last weekend.
The 21-Test flyer will line up at outside centre, replacing the injured Ben Tapuai (collarbone), while utility back Ben Lucas will start at flyhalf in place of Sam Lane (knee).
Reds coach Ewen McKenzie has also dumped Wallabies No 8 Radike Samo and named two ball scavengers in his backrow with rising flanker Liam Gill joining Beau Robinson, and Scott Higginbotham moving from No 6 to the back of the scrum.
McKenzie has also made three changes to his bench with forwards Adam Wallace-Harrison and Eddie Quirk coming in for Van Humphries (arm) and Samo, and Wallabies centre Anthony Faingaa making his return from a foot injury.
Ioane, who turned his back on a $1 million per year offer from Japan last year, said he was proud to notch his 50th cap in a crucial match for the battling Reds.
"I re-signed last year knowing Queensland was where I wanted to be so it's a great moment for me to reach the milestone for the Reds," he said.
"Hopefully we can celebrate the night with a win."
Teams:
15 Hadleigh Parkes, 14 George Moala, 13 Rene Ranger, 12 Ma'a Nonu, 11 Rudi Wulf, 10 Gareth Anscombe, 9 Piri Weepu, 8 Peter Saili, 7 Daniel Braid, 6 Luke Braid (captain), 5 Filo Paulo, 4 Ali Williams, 3 Charlie Faumuina, 2 Tom McCartney, 1 Tevita Mailau
Substitutes: 16 James Parsons, 17 Angus Ta'avao, 18 Liaki Moli, 19 Chris Lowrey, 20 Alby Mathewson, 21 Michael Hobbs, 22 Benson Stanley
Reds:
15 Luke Morahan, 14 Rod Davies, 13 Digby Ioane, 12 Mike Harris, 11 Dom Shipperley, 10 Ben Lucas, 9 Will Genia, 8 Scott Higginbotham, 7 Liam Gill, 6 Beau Robinson, 5 James Horwill (captain), 4 Rob Simmons, 3 James Slipper, 2 James Hanson, 1 Ben Daley
Substitutes: 16 Albert Anae, 17 Greg Holmes, 18 Adam Wallace-Harrison, 19 Ed Quirk, 20 Jake Schatz, 21 Nick Frisby, 22 Anthony Faingaa