The Knights sealed their status at the league's comeback specialists on Thursday night at Leichhardt Oval, overcoming a halftime deficit to win for the fourth time this year.
The victory secured the Knights their first minor premiership in either the NRL or NRLW, with Newcastle two wins clear of the second-placed Roosters early in the final round.
But victory did not come without some concerns for the defending premiers.
Southwell limped from the field in the 22nd minute after sustaining a leg injury when setting up the Knights' first try for Sheridan Gallagher eight minutes earlier.
Newcastle were confident the injury was only a cork, with the 18-year-old removed from the field as a precaution.
Gallagher was also hurt late in the match, limping with a knee injury after cleaning up a ball in her own in-goal.
The Knights winger remained on the ground in pain for several minutes as knee checks were conducted, before medical staff cleared her to continue.
With Southwell off the field, the Knights threatened to lose their way in the first half as Rikeya Horne and Rebecca Pollard scored to give the Tigers an 8-6 lead at the break, the second of those tries coming after a bust from Jakiya Whitfeld.
But just as they did against North Queensland, Brisbane and Canberra in recent week, the Knights were able to finish stronger.
The game swung early in the second half when Caitlan Johnston forced an error from the Tigers' Brooke Talataina.
From the scrum, Tamika Upton put Abigail Roache through a hole to go 60 metres to score. The Tigers were never really back in the match.
Another try came to Roache after a Nita Maynard break, and the centre was in the action again when she made a 70-metre intercept from which Yasmin Clydsdale profited in ther 57th minute.
The win means Newcastle will enter next week's semi-final on a seven-game win streak, with a match against the fourth-placed finisher looming.
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