The Waratahs claimed a bonus point in their four tries to nil victory in their biggest win over the Reds in Super Rugby.
The Sydneysiders finished the regular season seven points clear at the top of the standings and will now have a week off before hosting a semi-final for the first time.
The momentum is building for the Waratahs as they chase their first Super Rugby title and coach Michael Cheika was able to rest key player Israel Folau from the Australian derby with the Reds.
In Folau's absence his Wallaby team-mate Kurtley Beale was outstanding scoring two tries and having a hand in another in an impressive game as playmaker.
The Waratahs' other try-scorers were fullback Jono Lance and scrumhalf Nick Phipps with flyhalf Bernard Foley kicking four conversions and two penalties.
The Reds only points came from a penalty in the fourth minute from Mike Harris.
New Zealand referee Mike Fraser pulled out the yellow card twice - sending Waratahs prop Sekope Kepu to the sin-bin for punching Beau Robinson, while Reds' replacement Sam Johnson was shown yellow for a lifting tackle on Beale.
The Reds, who failed to reach the playoffs for the first time since their 2011 championship-winning season, lost three players through injury during the match - Ben Lucas, Ben Tapuai and Ben Daley.
It was the Reds' biggest loss to the Waratahs in 19 seasons of Super Rugby and their lowest score at Suncorp Stadium.
"It was good to put a few tries on and keep them try-less so we have a week off now but Queensland came out really tough tonight," said Waratahs skipper Michael Hooper.
"It was a good test for us tonight, they have a good set-piece so we can really build off this game."
Reds skipper James Horwill said everything was going the Waratahs' way to win this season's Super Rugby title.
"They have pretty much a full list of players to choose from and they don't have to travel if they keep on winning so the ball is in their court and they have a lot of advantages," said Horwill.
Scorers:Waratahs:
Tries: Jono Lance, Kurtley Beale (2), Nick Phipps
Conversions: Bernard Foley (4)
Penalties: Foley (2)
Reds:
Penalty: Mike Harris
Teams:
Reds:
15 Mike Harris, 14 Rod Davies, 13 Samu Kerevi, 12 Ben Tapuai, 11 Lachie Turner, 10 Ben Lucas, 9 Scott Gale, 8 Jake Schatz, 7 Beau Robinson, 6 Curtis Browning, 5 James Horwill (captain), 4 Rob Simmons, 3 Greg Holmes, 2 James Hanson, 1 James Slipper
Substitutes: 16 Saia Fainga'a, 17 Ben Daley, 18 Albert Anae, 19 Dave McDuling, 20 Liam Gill, 21 Sam Johnson, 22 Jamie-Jerry Taulagi, 23 Chris Kuridrani
Waratahs:
15 Cam Crawford, 14 Alofa Alofa, 13 Adam Ashley-Cooper, 12 Kurtley Beale, 11 Rob Horne, 10 Bernard Foley, 9 Nick Phipps, 8 Wycliff Palu, 7 Michael Hooper (captain), 6 Stephen Hoiles, 5 Kane Douglas, 4 Will Skelton, 3 Sekope Kepu, 2 Tatafu Polota-Nau, 1 Benn Robinson
Substitutes (one to be omitted): 16 Tolu Latu, 17 Jeremy Tilse, 18 Michael Ala'alatoa, 19 Jacques Potgieter, 20 Mitchell Chapman, 21 Pat McCutcheon , 22 Brendan McKibbin, 23 Jono Lance, 24 Taqele Naiyaravoro