Michael Cheika's men put in a strong second-half performance in Sydney to secure a maximum five-point return and secure their place as the number one side with a week to spare.
Victory means the Waratahs are guaranteed a home semi-final and an extra week off heading into the play-offs.
A tight first half saw the hosts go in only 11-9 to the good, but five tries in the second period saw them run out comfortable winners, with Israel Folau predictably among those to cross for his12th score of the season.
Elsewhere, the Cheetahs ended the Sharks hopes of finishing first, courtesy of a 27-20 upset in Bloemfontein on Saturday.
The Cheetahs climbed off the bottom of the table, handing the dishonour of last place to the Melbourne Rebels, who were beaten 34-17 by the Lions in Johannesburg on Friday.
Behind the Waratahs in second are the Crusaders, who claimed a 21-13 win over the Blues on Saturday, while the Western Force won their all-Australian Conference clash with the Queensland Reds 30-20.
Other results saw the Stormers beat the Bulls 16-0, while the Chiefs ran out 24-16 victors against the Hurricanes.