The Dogs steamrolled all through Souths in the opening stanza, dominating possession with 63 per cent of the footy and making twice as many metres as their opponents in the opening 40 (1016-541 metres).
Centre Josh Morris celebrated his 200th NRL game with a first-half double while the blue and white big men were unstoppable in the middle of the park.
Don't miss the blockbuster battle this weekend as ANZ Stadium's two long-term home clubs meet on Good Friday!
The Rabbitohs clearly missed the impact of Sam Burgess, who was never seriously likely to take his place five days after being stretchered off the SCG with a neck injury and sent to hospital, while they also lost fleet-footed winger Alex Johnston before kick-off.
The first half was the most one-sided 40 minutes of season 2016 so far as Canterbury rolled through the Bunnies with consummate ease.
James Graham churned through more metres (151) than all six members of Souths' entire starting forward pack combined (144) with Bunnies prop Dave Tyrrell notching 22 tackles and not a single carry.
The Dogs attacked Souths' left edge in the early exchanges and it paid off early when a Reynolds cutout to Chase Stanley resulted in a Sam Perrett kick infield for Will Hopoate to touch down.
A slick step from halfback Moses Mbye cashed in on a drop-out forced by a Reynolds kick shortly after and 200-gamer Morris scored his first in the 16th minute following a quality offload under pressure from Tony Williams.
Hooker Craig Garvey went himself shortly after to keep the Dogs in front of the clock and Morris bagged his double in unusual fashion when Paul Carter tried to offload as he was being forced back in-goal and lost control of the ball.
Sam Perrett cashed in on a simple overlap to make it 32-0 after 30 minutes and although Souths finally had a couple of good sets to finish the half they twice lost the ball while on the attack to struggle into the sheds without further damage.
The Bunnies managed to get back into the grind after the half-time break but still couldn't catch a break while attacking, despite forcing consecutive goal-line drop-outs.
Instead next points extended Canterbury's lead via an exquisite Mbye cut-out for a leaping Curtis Rona to make it 36-0 at the three-quarter mark.
Souths clawed a couple back as impressive rookie half Cody Walker combined with Luke Keary to create a few opportunities; a jinking cross-field run and flick pass from Keary set up a Michael Oldfield four-pointer then a Walker pass put Chris Grevsmuhl over.
Canterbury though managed one more try, through Chase Stanley, to complete a 42-12 rout that consigns the Rabbitohs to back-to-back losses and helped the Bulldogs join the Storm at the top of the ladder with three wins.
Canterbury Bulldogs 42 (Josh Morris 2, Will Hopoate, Moses Mbye, Craig Garvey, Sam Perrett, Curtis Rona, Chase Stanley tries; Moses Mbye 5 goals) def South Sydney Rabbitohs 12 (Michael Oldfield, Chris Grevsmuhl tries; Damien Cook 2 goals) at ANZ Stadium. Half time: Canterbury 32-0. Crowd: 38,192
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