Waratahs have made eight changes as they look to stop Griffith's winning run.
The Blacks have won their last five games to jump into third place on the Southern Inland ladder.
However they face their biggest test yet up against the premiers who are on an 10-game streak of their own at Exies Oval on Saturday.
The Wagga side have welcomed back some of their best but still have plenty of quality on the sidelines.
Captain Tim Corcoran and centre partner Joe Reynolds will both miss the clash while Xavier Chigwidden and James Grimmett are still sidelined with injury.
It means Dan Selmes returns at inside centre while Blake Hart shifts to outside centre with George Mallat moving to fullback.
Morgan Jones comes onto the wing with Sam Hobbs back at halfback.
There's even more changes in the forward pack following a 48-31 win over Leeton last week.
Sam Bunny, James Whiteley, Charlie Sykes and Harry Cook all come back into the side with James Daley switching to hooker.
Kurt Holzl, Bede Funnell, Sam O'Leary and Michael Allmark all make way.
Co-coach Michael Davis admitted the club had plenty of tough decisions to make.
"We're probably two forwards and four backs short," Davis said.
"There is a lot of stuff happening work-wise for blokes and it's a bit unsettled at the moment and next week is probably no different but you have to play who you've got."
However he's confident they can overcome it in the big clash and believes defence will be the key.
He wasn't thrilled by how many points the side let in last week and is looking for it to improve swiftly.
"It will be built on defence," Davis said.
"If you give them a sniff they will just keep coming and hopefully defensively we can shut them down.
"We're pretty confident in attack so attack will play a big part."
Griffith provided Waratahs with one of their biggest tests earlier in the year.
Waratahs managed to rally to score a 38-30 win and the Blacks are in better form now.
"We're expecting a very tough game," Davis said.
"They will be fired up after a narrow loss in the first round and we're expecting no difference."
Griffith rallied late to take a seven-point win over Albury last week.
However the Blacks head into the clash with Suliano Kabara after he was suspended for two weeks over a lifting tackle charge.
He'll miss games against the two top sides.
Blacks coach Craig Morriss is looking for the side to lift for another big challenge.
"It will be the test of all tests," Morriss said. "They are the pinnacle of the competition and have been for a couple of seasons now.
"We went close in Wagga but will be looking to take that one step further.
"We have come a long way since then."