The Tahs were in irresistible form, racing away from the Highlanders in the second half after shading them 11-9 at halftime.
It was the Waratahs' sixth straight victory and their biggest-ever win over the Highlanders to underline their favourites tag for this year's Super 15 title.
The Waratahs are clearly enjoying their rugby under coach Michael Cheika as they chase their first Super Rugby championship after being runners-up in 2005 and 2008.
Their bonus-point victory took them an unassailable seven points ahead of the Canterbury Crusaders and Coastal Sharks on the overall standings heading into next weekend's final regular round of the season.
The win also means the Waratahs will host a semi-final and are just one game away from staging this year's Super 15 final given their guaranteed top ranking.
The Waratahs have all the title momentum and look every inch a championship side in the making with tries from Rob Horne, Israel Folau, Sekope Kepu, Nick Phipps, Jacques Potgieter and winger newcomer Taqele Naiyaravoro.
Fly-half Bernard Foley kicked four conversions and two penalties to swell his season haul to 199 points.
The Highlanders, who will play the Crusaders for the New Zealand conference title in Christchurch next weekend, were in the game at halftime after three penalty goals from Lima Sopoaga got them within two points of the Waratahs.
But they didn't register another point until a kick and chase try from replacement Phil Burleigh with seven minutes left.
The Waratahs had the last word with the hulking Naiyaravoro scoring his team's sixth try in the final minute.
The Waratahs had plenty of outstanding performers, headed by Wallabies Kurtley Beale and Foley, while South African lock Potgieter was a tower of strength in the forwards.
Folau scored his 12th try of the season and coach Cheika took the opportunity to clear his replacements bench with victory assured inside the final 20 minutes.
"Everyone needs to be doing their jobs well at this point of the season and we did that tonight, six tries to one, can't complain," Waratahs skipper Michael Hooper said.
The Waratahs finish off their regular season with an anticipated feisty Australian derby against the Reds in Brisbane.
"It's always tough playing up there and we look forward to that and with the last round game of the year we need guys to be fit and ready to go," Hooper said.
Otago skipper Nasi Manu said poor execution had cost his side their chance against the rampant Waratahs.
"There
were crucial errors at crucial times and there were opportunities, but
one pass wasn't quite accurate or there was a dropped ball," Manu said.
Scorers:
Waratahs:
Tries: Rob Horne, Israel Folau, Sekope Kepu, Nick Phipps, Jacques Potgieter, Taqele Naiyaravoro
Conversions: Bernard Foley (4)
Penalties: Foley (2)
Highlanders:
Tries: Phil Burleigh
Conversions: Hayden Parker
Penalties: Lima Sopoaga (3)
Teams:
Waratahs
15 Israel Folau, 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 (c), 6 Stephen Hoiles, 5 Kane Dougles, 4 Jacques Potgieter, 3 Sekope Kepu, 2 Tatafu Polota-Nau, 1 Benn Robinson.
Substitutes (from): 16 Tolu Latu, 17 Jeremy Tilse, 18 Paddy Ryan, 19 Will Skelton, 20 Mitch Chapman, 21 Pat McCutcheon, 22 Brendan McKibbin, 23 Jono Lance, 24 Taqele Naiyaravoro, 25 Cam Crawford
Highlanders
15 Ben Smith, 14 Richard Buckman, 13 Malakai Fekitoa, 12 Shaun Treeby, 11 Patrick Osborne, 10 Lima Sopoaga, 9 Aaron Smith, 8 Nasi Manu (captain), 7 Shane Christie, 6 Elliot Dixon, 5 Joe Wheeler, 4 Tom Franklin, 3 Ma'afu Fia, 2 Brayden Mitchell, 1 Kane Hames
Substitutes: 16 Ged Robinson, 17 Matias Diaz, 18 Chris King, 19 Josh Bekhuis, 20 Lee Allan, 21 Fumiaki Tanaka, 22 Hayden Parker, 23 Phil Burleigh