Former rugby league star Regan Grace will make his Wales debut against the Reds after being named by coach Warren Gatland in the starting side on Wednesday.
The ex-St Helens wing represented Wales six times in the 13-man game before switching codes in 2022, but serious injuries have hampered him since.
Prop Kemsley Mathias, hooker Evan Lloyd, No 8 Mackenzie Martin and centre Eddie James will also have their first Wales starts on Friday in Brisbane against the Super Rugby team.
Replacement hooker Efan Daniel is another in line for a debut, off the bench, in a new-look team after consecutive test defeats to the Wallabies.
Lock Cory Hill will captain the side with Dewi Lake, who skippered Wales in both tests against Australia, not in the 23.
"We said that we want the players that have come out here on tour to have an involvement, whether that is starting or in the 23," said Gatland.
"That was always the plan. Unfortunately, a few players miss out due to injury, but this game against the Reds gives a number of others an opportunity to go out and put in a performance."
With the likes of Liam Wright and Tate McDermott on Australia duty against Georgia on Saturday, the Reds feature fellow Wallabies James O'Connor and Jock Campbell.
It is the Reds' first home clash against a national side in 20 years and their first with Wales since 1991, when a young John Eales was in the side that won 35-24.
WALES (15-1)
Cameron Winnett; Rio Dyer, Nick Tompkins, Eddie James, Regan Grace; Sam Costelow, Gareth Davies; Mackenzie Martin, Taine Plumtree, Christ Tshiunza; Cory Hill (capt), Matthew Screech; Archie Griffin, Evan Lloyd, Kemsley Mathias
REPLACEMENTS: Efan Daniel, Corey Domachowski, Harri O'Connor, Dafydd Jenkins, Tommy Reffell, Kieran Hardy, Ben Thomas, Mason Grady
QUEENSLAND REDS (15-1)
Jock Campbell; Floyd Aubrey, Tim Ryan, Dre Pakeho, Mac Grealy; James O’Connor, Louis Werchon; Joe Brial, John Bryant, Seru Uru; Ryan Smith, Connor Vest; Jeffery Toomaga-Allen, Richie Asiata, Sef Fa'agase,
REPLACEMENTS: George Blake, Matt Gibbon, Massimo De Lutiis, Josh Canham, Connor Anderson, Will Cartwright, Mason Gordon, Lachie Anderson