The Rebels host the Reds on Friday night at AAMI Park, with both teams banking two wins against a loss to open the season, with Queensland ahead in third spot on points differential.
A late hero with his defensive efforts and try assist in the win over the Chiefs, 19-year-old McLaughlin-Phillips will start at five-eighth ahead of Tom Lynagh, who has been included on the bench.
He will be joined there by Wallabies utility Jordan Petaia, who returns from concussion, while Fijian prop Peni Ravai will start in place of suspended Sef Fa'agase.
Reds coach Les Kiss says the change at 10 is more about managing Lynagh, who had an injury-hit preseason and was floored by a big tackle last week.
"We're very fortunate to have the options we do at No.10,'' Kiss said.
"Tom has had a couple of good games starting, and this is an opportunity for Harry to start.''
The coach rated the Rebels' forward pack, led by Tupou, who have steered the team to two successive wins.
"It's a big challenge. As a forward pack, the Rebels have found their mojo and allowed their backline to play," Kiss said.
Tupou came off the bench in their win over Moana Pasifika and was crucial in winning scrum penalties and gaining ascendancy at set pieces.
Melbourne have returned game-breaker Andrew Kellaway to fullback, with Glen Vaihu lining up on the wing.
Another ex-Red, Filipo Daugunu, will start in the centres.
In the late game on Friday night, the Western Force will be desperate to bank their first win when they take on Moana in Perth.
Force coach Simon Cron has relegated prized recruit Nic White to the bench in favour of fellow Wallabies halfback Issak Fines-Leieiwasa.
Vice-captain Michael Wells will miss with a knee injury, with Tim Anstee named at blindside flanker.
Joining the Force on an injury-cover contract, flanker Reed Prinsep will bring some experience to the bench after notching 73 Super games for the Hurricanes.
Moana Pasifika have named former Wallabies duo Christian Lealiifano and Sekope Kepu in their starting line-up.
The ACT Brumbies have rotated their front row to face the Highlanders in Dunedin on Saturday, bringing in youngsters Billy Pollard and Blake Schoupp, while lock Cadeyrn Neville returns after a cut head.
A concussed Luke Reimer has been replaced at open-side flanker by Jahrome Brown.
The NSW Waratahs have lost star fullback Max Jorgensen to a hip injury, with Mark Nawaqanitawase named at 15 to face the Blues in Sydney on Saturday night.
Dylan Pietsch returns from an eye injury to replace Nawaqanitawase on the wing, while hooker Julian Heaven is set for his first Super start.
The Waratahs have three injured hookers, including Test rake Dave Porecki, with coach Darren Coleman promoting Jay Fonokalafi from the Two Blues in the Shute Shield to the bench.
In a much-needed boost after their late heartbreak against the Highlanders, back-row enforcer Lachie Swinton is set for his first match of the season.
