The Knights confirmed on Monday that Ponga had sustained a Lisfranc injury in his right foot in Sunday's 36-12 loss to Canterbury.
While Newcastle did not specify a timeline for Ponga's return, the club's football boss, Peter Parr, said it would be "months rather than weeks" until the No.1 was back on the field.
"Kalyn had scans on Monday morning confirming he has a lisfranc injury," Parr said.
"The next steps will include seeing a surgeon and setting up an injury management program."
A hobbling Kalyn Ponga was unable to finish Newcastle's clash with Canterbury on Sunday. (Mark Evans/AAP PHOTOS)
Then-Canterbury prop Luke Thompson and Parramatta forward Wiremu Greig suffered a similar injury last year.
Thompson missed 20 weeks of NRL action, while Greig was back within nine - indicating the uncertainty facing Ponga and the Knights as they plot a path back to full fitness.
The loss of Ponga comes with Newcastle struggling to rediscover the electrifying form which catapulted them into last year's finals series.
Rookie David Armstrong played in NSW Cup at fullback last week, while coach Adam O'Brien also has experienced campaigner Dane Gagai as an option to fill the No.1 jersey.
Ponga's injury is also a major setback for Queensland coach Billy Slater as he looks to maintain the Maroons' Origin stranglehold.
Ponga sat out last year's series following repeated concussion issues, but his form at the back end of last season - which led to him being awarded the Dally M Medal - had created a welcome headache for Slater.
The Maroons coach had been mulling how to fit Ponga and electric Brisbane No.1 Reece Walsh into the same Queensland side, but that now appears a moot point.
