Scrumhalf Ryan Lonergan will captain the side, with Lachie Hooper's debut off the bench against the British and Irish Lions on Wednesday.
It will be the 21-year-old's first chance to line up professionally alongside big brother and Wallaby Tom, who departs for England's Exeter Chiefs in the off-season.
The Brumbies humbled the Lions 14-12 on their last visit 12 years ago, becoming the first Australian club to beat them since 1971.
Wary of a repeat, the Lions have reinstalled lock and captain Maro Itoje and will start Bristol firebrand Ellis Genge in the front row, while Ireland's former Brumbies winger Mack Hansen earns a homecoming from the bench.
"This year they were the leading Australian team in Super Rugby (making the semi-finals), so we are fully aware of the challenge in front of us," Lions coach Andy Farrell said.
Brumbies coach Stephen Larkham hailed the talents of the younger Hooper, who he watched and helped develop over the years through the ACT rugby system.
"We really wanted them to be here together, and we really wanted them to play together, and we just didn't get the opportunity this year," he said.
"But hopefully everything goes to plan and they get on the field and they really enjoy not only the moment, but the way that we play the game."
Tom, 24, returns to the starting side after playing 12 minutes in the Wallabies' ugly 21-18 victory over Fiji in Newcastle on Sunday, but several big-name Test players will be absent, including Rob Valetini and captain Allan Alaalatoa.
"We've been planning for this for a while, and yeah, second row was certainly a position that we were a little bit light-on," Larkham said.
Taming the Lions will be a tough ask for Larkham's inexperienced side.
The tourists posted half-centuries against the Queensland Reds and the Force, and despite a strong performance from the NSW Waratahs still prevailed 21-10 in Sydney.
Looking at the scorelines, Larkham conceded it was hard to argue that the Lions had yet to face a proper challenge in Australia.
"Although I thought the Waratahs were pretty good on the weekend," he said.
"I thought it was a very impressive game against the Reds.
"We've learned a lot from that. We get the benefit of playing last so we get to see three of their games in Australia, they've had their Argentinian game as well, so we've sort of studied them quite closely.
"We feel that we've had a pretty good run at our preparation compared to the other teams.
"They (the Waratahs) came into the game with some tactics that worked pretty well, and we've learned a little bit out of the Waratahs game as well."
Wednesday's game will also serve as a Brumbies farewell for Jack Debreczeni and Ben O'Donnell, who will join French side Aurillac on a two-year deal.
BRUMBIES: Lington Ieli, Lachlan Lonergan, Rhys van Nek, Lachie Shaw, Cadeyrn Neville, Tom Hooper, Rory Scott, Tuaina Taii Tualima, Ryan Lonergan, Declan Meredith, Corey Toole, David Feliuai, Ollie Sapsford, Ben O'Donnell, Andy Muirhead. Bench: Liam Bowron, Cameron Orr, Feao Fotuaika, Lachie Hooper, Luke Reimer, Harrison Goddard, Jack Debreczeni, Hudson Creighton
LIONS: Ellis Genge, Dan Sheehan, Tadhg Furlong, Maro Itoje, Joe McCarthy, Ollie Chessum, Tom Curry, Jack Conan, Jamison Gibson-Park, Finn Russell, James Lowe, Bundee Aki, Garry Ringrose, Tommy Freeman, Blair Kinghorn. Bench: Ronan Kelleher, Andrew Porter, Will Stuart, Josh van der Flier, Henry Pollock, Alex Mitchell, Marcus Smith, Mack Hansen
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