Brisbane led 22-0 early and Souths hinted at a comeback when they clawed their way back to 28-12 with 23 minutes remaining, before two second-half tries in three minutes blew the Broncos' lead out to 40-12 and the game was over.
Brisbane provisionally move back to the top of the NRL ladder with just their second win in five games.
Without Greg Inglis, a tired looking Souths struggled to match Brisbane's finesse and power from the start.
An Adam Blair offload put Milford in the clear before Brisbane spread it wide for Jordan Kahu to score to open the scoring in the seventh minute.
Corey Oates then raced 95m after collecting an Adam Reynolds kick and brushing off makeshift fullback Dylan Walker as he planted the ball. From the ensuing kickoff, Milford skipped his way through the line before passing on to Jack Reed who dished off for Hunt to score.
When Kahu scored his second try in the 25th minute, the visitors led 22-0.
Chris Grevsmuhl claimed one back for Souths in the 29th minute to give them some hope.
Hunt scored his second in the 46th minute before Luke hit back 10 minutes later to the delight of the disappointing 12,036 crowd.
But Brisbane then clicked into gear again to blow out the scoreline on the back of two tries to Milford and another to Hunt in the final 16 minutes.
The win was Broncos coach Wayne Bennett's first over his Souths' opposite Michael Maguire in six attempts. The scoreline was a massive change to the Rabbitohs' 36-6 win way back in round one.
Sutton limped off in the 50th minute. Luke's report for a shot on Oates came 10 minutes later.
Bennett said defence was the most pleasing thing about Brisbane's win.
"That is what we have been working for, to play games with good execution like that and we know the benefits when we do and the repercussions when we don't," he said.
"Our defence is our strength. Our attack has been on and off at different stages but out defence has been pretty constant all year. The first game against South Sydney and the one against Manly are the only blow-out scores we have had all year.
"The defence kept us in the game tonight. When we were getting a bit untidy or under pressure, they just kept turning up and didn't let them score."
Maguire wasn't impressed with his side.
"We were poor, simple as that," he said.
"Our standards dropped throughout periods of the game. We didn't show the adversity I know that is in this team and we have to turn that around.
"I'm not really concerned about where that is (ladder position at the end of the round) - it's more about how we are playing.
"If we turn up like that and have that performance, of course that is going to happen. It is in our hands about how we go about things.
"Unfortunately, we let ourselves down tonight and that isn't acceptable."
- AAP
