On a night Thomas Jenkins continued his incredible tryscoring exploits with a hat-trick at CommBank Stadium, Penrith re-established a three-win buffer at the top of the ladder.
Jenkins now has 25 tries through 16 appearances this year and is a genuine chance of breaking a 91-year record for the most tries scored in a season, currently held by Dave Brown who crossed 38 times for Easts in 1935.
His hat-trick along with the insatiable output of workhorse fullback Dylan Edwards were critical to the victory as the ladder-leading Panthers snapped a two-game losing streak on Friday.
Edwards chalked up 228m from 20 carries for a Penrith side missing Isaah Yeo, Nathan Cleary and Liam Martin to NSW State of Origin selection.
Souths were only without Cameron Murray as a result of Origin duty, but there will be concerns about the availability of Walker for next Sunday's meeting with Newcastle.
Walker was sent to the bin after playing the ball in the 11th minute and then sparking an all-in melee after aiming a kick at stand-in Panthers halfback Jack Cogger.
Rabbitohs rookie Dayne Jennings had crossed in the right corner on the ensuing tackle, but his try was chalked off as Walker was sent to the bin.
Prop Junior Tatola was also placed on report in the second half for a high shot on Penrith five-eighth Jack Cole.
The Panthers hit the front through a sidestepping Edwards before Walker's sin-binning allowed Penrith to push further ahead through Liam Henry.
Tries for Jennings and Ed Kosi cut the Panthers' halftime lead to 12-10, but some brilliance from Jenkins helped Ivan Cleary's men kick clear in the second half.
The winger climbed high over Jennings to claim a Cogger kick and then fended off Jack Wighton in the corner to grab his first.
His second was much controversial, appearing to have lost control of the ball in the act of grounding. Referee Adam Gee sent it up as a try and with bunker camera angles inconclusive the four-pointer was given.
Billy Phillips barged over next for the Panthers before Jenkins tip-toed down the sideline to touch down for his hat-trick.
The winger's third equalled the record for most tries for Penrith in a season since Rhys Wesser's haul of 25 in 2003.
Cogger was sent to the bin for a high shot on Ashton Ward in the final 10 minutes with Latrell Siegwalt claiming a consolation try for the Bunnies.
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