Newcastle confirmed on Friday that Sharpe would be left on ice for Saturday's bumper clash with the Warriors, after he failed to overcome a knee injury.
It means the 21-year-old will join Kalyn Ponga and Dylan Brown on the sidelines, leaving Newcastle without their first-choice fullback and two halves.
Newcastle had initially hoped Sharpe could return to the No.6 jersey this weekend, but he was unable to get through training late in the week.
There had also always been some thought towards a conservative approach, after Sharpe suffered damage to his posterior cruciate ligament in Las Vegas in round one.
It means Tyson Gamble will return to first grade to partner Smith in the halves, after playing just six games of NRL last season.
But after scoring more points in their two first-up wins of this year than the last five games of 2025, Newcastle are confident their attack will hold up.
"Tyson and Sandon (have spent) plenty of time together, particularly pre-Christmas, when we didn't have the international guys," Knights coach Justin Holbrook said.
"That's why, so everyone is clear what they have to do when they do get called upon, so we don't miss a beat.
"Tyson is a really experienced player, and had a really good pre-season and played really well in NSW Cup, so he will slot in there."
While Gamble's call-up is something of a reprieve after he was stuck behind Brown, Sharpe and Smith at the start of the year, Smith's rise to No.7 is equally notable.
After looming as Sam Walker's long-term halves partner at the Sydney Roosters, he was dropped for Hugo Savala last year, then left after Daly Cherry-Evans' arrival.
Smith landed in Newcastle eying off a chance, before narrowly being beaten for a spot in the halves for the opening round, with Sharpe partnering Brown.
He was then thrown on the field after 20 minutes in Vegas, and is now the Knights' chief playmaker with Brown expected to miss four games with his knee injury.
"That's rugby league, honestly. It's a massive roller-coaster," Smith said.
"I think there's a quote out there that a week in rugby league feels like a lifetime, and it's honestly so true.
"It's been a bit of my career over the past few years, so I've been able to just learn to adapt, and you always have to stay ready.
"Honestly, you do never know what's going to happen."
The undefeated Warriors have received a boost, with NSW prop Mitchell Barnett cleared to return from his ACL rupture, but centre Adam Pompey will stay in Auckland for the birth of his first child.
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