A Cody Walker masterclass led the Rabbitohs to a 40-28 win over the Knights at McDonald Jones Stadium as David Klemmer was sent off in a fiery finish to the night.
With Damien Cook and Cameron Murray on Origin duty, Walker took charge with two tries, two try assists and 95 run metres as the Bunnies chalked up their ninth win of the season.
Already missing their Blues brothers, the Rabbitohs lost Mark Nicholls and Alex Johnston to injury in the lead-up to the game, and then had Lachlan Ilias go off after a head clash with team-mate Tevita Tatola in the opening minute of the match.
Despite the early setback the Rabbitohs opened the scoring in the 10th minute when Cody Walker scooped up a loose pass, crashed into team-mate Thomas Burgess and crashed over. The try was sent to the bunker to check for obstruction by Burgess but the green lights were shown and Souths led 6-0.
The home side hit back in the 15th minute when a long Tyson Frizell break was followed up by a crisp right-side raid which Dom Young finished off.
A rare try to prop David Klemmer in the 19th minute helped the Knights extend the lead before Bradman Best celebrated his return from an elbow injury with a four-pointer courtesy of a sensational try assist by Edrick Lee, who flew high to bring down a bomb and then delivered a flashy flick pass to his centre.
The Bunnies' left side clicked into gear in the 31st minute when Walker and Latrell Mitchell combined to put Richie Kennar over to cut Newcastle's lead to 16-12.
Just three minutes later Kennar had a double courtesy of a deft left foot kick by Walker and Mitchell's sideline conversion gave the visitors the lead.
With half-time approaching and the Knights attacking, Walker came up with a massive play when he intercepted a Mat Croker pass and sprinted 85 metres to score his second of the night.
A mistake early in the second half by the Knights handed the Rabbitohs field position and they capitalised when Walker put the ball on a platter for Kennar to complete the first hat-trick of his career.
Come the 53rd minute and Tatola joined the tryscoring action with the sixth try of his 108-game career after Tex Hoy had failed to ground a Walker grubber and the prop pounced.
A superb long ball from Adam Clune put Lee over in the 59th minute as the Knights pulled back to 34-22 but when the Rabbitohs chanced their hand on the fifth tackle and put Jaxson Paulo over in the right hand corner the margin was back out to 16.
Mitch Barnett pulled one back for the Knights with 11 minutes to play to make it 38-28 and a short dropout gone wrong by Souths in the 75th minute gave Newcastle a shot but desperation defence by Kodi Nikorima denied Best from close range.
In a fiery end to the match Klemmer and Kaeon Koloamatangi squared off before the Knights prop was marched in the next set for contact to the head of a player on the ground.
Souths halfback Lachlan Ilias was forced off for a HIA in the first minute and did not return.
Latrell Mitchell was placed on report in the 18th minute for a high tackle on Knights winger Dom Young, who was sent for a HIA after the incident.
David Klemmer's try in the 19th minute was just the fifth of his NRL career and his first since round 25, 2017 for Canterbury against Gold Coast.
Souths prop Thomas Burgess went on report in the 28th minute for a high shot on Daniel Saifiti.
The Rabbitohs have won 12 of their past 14 games against the Knights.
Thomas Burgess was named on the bench but entered the fray in the first minute after Lachlan Ilias' head knock. The Englishman responded with a mammoth 119 running metres in the opening 40 minutes and finished the night with 194 metres.
Knights halfback Adam Clune left the field for a HIA in the 42nd minute. He passed and returned to the game.
Knights hooker Jayden Brailey took the field at the start of the second half in his first match of the season having overcome an achilles injury.
Newcastle have not beaten a top-eight opponent all season.
Edrick Lee has scored 20 tries in 19 games at McDonald Jones Stadium
Daniel Saifiti and David Klemmer led the way up front for the Knights with 311 running metres between them.
Pasami Saulo left the field with nine minutes to play for a HIA.
Plays of the Game
Dom Young came up with two cracking plays in the space of two minutes, denying Kodi Nikorima at one end with a last-ditch tackle and then finishing off a sweeping movement to score in the corner in the next set of six. Young's speed came to the fore in the chase on Nikorima and then after Tyson Frizell had busted the Bunnies up the middle it was Young finishing off slick passing from Adam Clune and Anthony Milford to grab Newcastle's opening try. Coming off his hat-trick last week against the Titans it continued a rich vein of form for the 20-year-old flyer.
Cody Walker has a knack of coming up with a big play when his team needs it and he capped a brilliant first half with a runaway intercept just as the Knights were threatening to score. The mercurial No.6 read the play beautifully and cruised 85 metres to take Souths out to an eight-point lead at the break.
The Knights head to 4 Pines Park to take on the Sea Eagles in Round 18 and will be hoping to have Origin reps Kalyn Ponga and Dane Gagai back on deck.
The Rabbitohs will be hoping an eight-day turnaround gives Alex Johnston (quad), Mark Nicholls (concussion) and Lachlan Ilias (head knock) a chance to get up for the clash against the Bulldogs at Accor Stadium.