It is now impossible for the Knights, who sat 14th on the ladder after 19 rounds, to be ousted from the top eight with a week to play in the regular season.
Ponga guided the Knights to Sunday's home victory, scoring their first try, putting them in position for their second and setting their fourth up as the Knights scored five unanswered four-pointers after halftime.
But the Newcastle captain lay in pain on the ground after receiving a late hit from Sharks centre Jesse Ramien as he passed the ball ahead of Newcastle's fourth try in the final 20 minutes.
Ponga surrendered goal-kicking duties to Dane Gagai but tried to play through the discomfort.
When Greg Marzhew crossed and put the result beyond doubt in the final 15 minutes, Ponga came off and went straight up the tunnel for a medical assessment.
He will go for scans on Monday but the initial diagnosis is an acromioclavicular (AC) joint injury.
Any long-term absence would be disastrous for Newcastle, given Ponga's pivotal role in resurrecting their season.
The Knights are already missing the other key cog in their attack, halfback Jackson Hastings, whose ankle injury forced him out of a second consecutive game on Sunday.
Despite the big defeat, the Sharks have likely done enough to seal a finals berth of their own.
They would only miss out on a top-eight finish if they lost big to Canberra next week, South Sydney beat the Sydney Roosters and North Queensland thrashed reigning premiers Penrith.
The lowest Newcastle can finish is sixth on the ladder, meaning they will host a home final for the first time since 2006 even if they lose to 16th-placed St George Illawarra next week.
After his opposite man Connor Tracey opened the scoring, Ponga shrugged out of a Matt Moylan tackle to level the scores 6-6 at halftime.
Ponga helped the Knights to their first lead of the afternoon when he beat five defenders and belted 50 metres on a kick return.
The Sharks' defence was still recalibrating when Bradman Best scythed through on the left for a try that confirmed all momentum for the Knights and they never looked back.
When Tyson Gamble looped a ball over on the right nine minutes later, lethal winger Dom Young had his first try.
And soon after, Newcastle closed in on a significant win as Ponga found Best with a cut-out pass.
