The Dragons had four players serving their one-game bans for a previous COVID breach and their makeshift centre pairing of Junior Amone and Corey Norman was targeted ruthlessly while Mitchell simply bullied the defence to the tune of two tries and 15 busts with Walker adding a try and four try assists of his own.
Broncos-bound halfback Adam Reynolds was also impressive with a try, two assists and seven goals while the Dragons were simply lacking in direction and experience.
Souths coach Wayne Bennett wasn't overly impressed with his team's performance.
"It was a bit all over the place - there was some really good footy and then some ordinary stuff and then some really good football," he said.
Mitchell is arguably in career-best form and Bennett believes he can help the third-placed Rabbitohs achieve their immediate goal of a top-four playoff berth.
"He's an X-factor regardless of who he plays for, he was in the Origin series, every teams needs that sort of player," he said.
"But we've got to have everyone else around him doing their jobs as well otherwise the X-factor doesn't come into play."
The Dragons looked to have scored after just one minute but Mat Feagai's effort was correctly overturned once the Bunker spotted a Norman knock-on in the lead-up, saving the blushes of Jaxson Paulo who spilled a regulation kick.
Instead it was Souths who quickly went two tries ahead as first Mitchell then Walker were able to isolate rookie centre Amone one-on-one for a 12-0 lead after 15 minutes.
Ben Hunt's boot dragged the Red V back into the match; his early grubber caught the Souths backs out of position for Billy Burns to touch down then a low cross-field kick bounced off Walker's fingertips for a grateful Tyrell Fuimaono to plant the ball down. He also nailed his third 40/20 of the season to claim a share of top spot in that category with Manly's Daly Cherry-Evans.
Souths, though, weathered that storm and pulled away again in the seven minutes before the break with Taane Milne then Jaydn Su'A getting through the Dragons' left-side defence, with the latter held up for an age by Norman before eventually fighting the ball to the ground for a 24-10 half-time advantage.
The Dragons were able to exert some pressure early in the second half but produced an awful kick chase that allowed Jaxson Paulo to run 40 metres, with the Red V forced to backpedal for an entire set in which Souths went the length and Josh Mansour scored at the end of it.
Burns slipped a wonderful offload in traffic for Tyrell Sloan to glide his way to the line with 15 minutes remaining but Souths finished like a steam train.
Reynolds produced a chip and chase for himself to score in the 69th minute then Mitchell bowled half the Dragons team out of the way in a monstrous run that scattered the defence and allowed Walker to slip a perfect inside pass for Jai Arrow to score in the 72nd, Keaon Kolomatangi crashed over three minutes from time and that man Mitchell carved over in the final minute to round out a dominant win.
Milne, Su'A and Fuimaono will all have a nervous wait for the charge sheet after being placed on report for dangerous tackles.
Cameron Murray will return from suspension for next Friday's Cbus Super Stadium showdown with Parramatta, a welcome return for a team that has been missing Campbell Graham, Liam Knight, Alex Johnston, Benji Marshall and Tevita Tatola.
"We had seven genuine first-graders out tonight, we've been in that situation for a long period of time - players missing with injuries, State of Origin commitments, resting and whatever," Bennett said.
"That's been our strength this year. The fact that the other players have turned up and put a great effort in for us.
"We'll get three or four of those players back next week, I hope, and the others will come back in the next few weeks so it's only going to strengthen us and make us better."