But the Knights have received welcome news on attacking livewire Fletcher Sharpe, who is on track to return from his knee injury against the Warriors this weekend.
Scans confirmed Ponga suffered a high-grade hamstring strain during the first half of Sunday's 36-16 thrashing of Manly, meaning he will miss between six and eight weeks.
It leaves the Queensland star with limited time to push his case for State of Origin selection on return, with the series opener scheduled for May 27.
Ponga missed last year's Origin decider through injury and will have to compete with both incumbent Hamiso Tabuai-Fidow and Brisbane ace Reece Walsh for Queensland's fullback spot.
Star playmaker Brown will spend four weeks on the sidelines with a grade-two medical cruciate ligament strain suffered late in the first half of Sunday's win.
"Yesterday was a tough, physical contest and the boys showed real grit to come away with a great win," said Knights football boss Chris James.
"Injuries are part of our game, and the character our group showed to fight through adversity says everything about the culture we are building."
The double blow came after Newcastle's other attacking weapon Sharpe went down with a posterior cruciate ligament injury in the round-one defeat of North Queensland in Las Vegas.
The injuries threatened to take the shine off a fantastic start to life under new coach Justin Holbrook, who has the 2025 wooden spooners 2-0 to begin the year.
But Sharpe is progressing well in his recovery and will on Tuesday be named in the halves alongside Sandon Smith for Saturday's first game in Newcastle this season.
"We've trained all through the pre-season together," Smith said.
Fletcher Hunt switched to fullback midway through the win over Manly and is the leading candidate to wear Ponga's No.1 jersey against the Warriors this week.
"He does a massive job for us. So I think that's next man up and that'll slot in really perfectly," smith said.
"We're keen to go home and rip into the Wahs."
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