Israel Folau will make his Super Rugby debut on Saturday when he pulls on the number 15 jersey against the Reds.
Alongside him, in-form youngster Tom Kingston earns a spot on the left wing with Wallaby Drew Mitchell completing the back three.
Fly-half Bernard Foley has recovered from an ankle injury to guide the backline that also features Adam Ashley-Cooper and Tom Carter.
Up front, prop Jeremy Tilse earns his maiden Super Rugby start, completing an otherwise all-Wallaby pack. Now in his eighth season with the 'Tahs, the 26-year-old prop's trial form made it hard for head coach Michael Cheika to overlook him.
"All the front rowers have made it very difficult for me to pick a starting team," said Cheika.
"Since I've been here Jeremy has been working like crazy, he's strong and fit and he's hungry. We need guys competing against each other to get us hardened for when we go out into the enemy territory, like on Saturday."
The side will be led for the first time by new skipper Dave Dennis who becomes the 164th player to captain New South Wales since 1882 and the 17th in Super Rugby.
The game is also head coach Cheika's first in charge but the former team-mate of Reds' coach Ewen McKenzie says he is relishing the prospect of facing up to arch-rivals Queensland.
"We know we're going into the lion's den for our first game but we're looking forward to it. There's a lot of self belief in the team," he said.
With three trial matches under his belt, Cheika believes Folau's past experiences from league and AFL will help him cope with the big occasion.
"It'll be a pressure cooker atmosphere but he's experienced that before so he'll be ready for it.
"A big part of going away from home is getting the fans against you and you've got to try and silence them by what you do on the field."
On the bench, Cheika has opted for a five-two forward-backs split, relying on halves Matt Lucas and Ben Volavola to cover the backline. If Lucas takes the field, he could make his Waratahs debut opposite his older brother Ben, the Reds scrum-half.
Waratahs: 15 Israel Folau, 14 Drew Mitchell, 13 Adam Ashley-Cooper, 12 Tom Carter, 11 Tom Kingston, 10 Bernard Foley, 9 Brendan McKibbon, 8 Wycliff Palu, 7 Dave Dennis (c), 6 Michael Hooper, 5 Kane Douglas, 4 Sitaleki Timani, 3 Sekope Kepu, 2 Tatafu Polota-Nau, 1 Jeremy Tilse.
Replacements: 16 John Ulugia, 17 Benn Robinson, 18 Paddy Ryan, 19 Mitchell Chapman, 20 Lopeti Timani, 21 Matt Lucas, 22 Ben Volavola.
Date: Saturday, 23 February
Venue: Suncorp Stadium, Brisbane
Kick-off: 19:40 (08:40 GMT)
Referee: Chris Pollock (New Zealand)
Assistant referees: Andrew Lees (Australia), Rohan Hoffmann (Australia)
Television match official: Steve Leszczynski (Australia)