The Terriers head to the Potteries looking to kick-start their season into life after taking just a point from the opening three games.
Wagner plans to ring the changes for a tie that would have brought a reunion with Tom Ince had the £10m summer departure to Stoke not suffered a hamstring injury.
“This is probably the most difficult draw we could face in the cup apart from the Premier League clubs,” said the Huddersfield chief.
“Stoke have a lot of very experienced and very good players who have played at the highest level.
“This doesn’t change the fact we want to be successful against them. To do this we will have to perform at our highest level, with fresh legs and a clear head as well.
“We know what we will face. They have a lot of options so we can’t focus on individuals. We have to focus on the team.”
Jonathan Hogg misses the trip through suspension following his red card in the goalless stalemate with Cardiff City at the weekend.
Chances are that the midfielder would have been left out anyway due to Wagner preferring to rotate his squad when cup ties come round.
Aaron Mooy, Steve Mounie, Florent Hadergjonaj and Mathias ‘Zanka’ Jorgensen are also expected to be among those left out with Saturday’s trip to Everton in mind.
Danny Williams is in line for his first outing since suffering a knee injury last February, while Erik Durm could also see action in a Town shirt for the first time having joined from Borussia Dortmund during the summer. Durm, a member of the Germany squad that won the 2014 World Cup, missed all last season with a succession of injuries.
Another ‘newcomer’ expected to start is Montpellier loanee Isaac Mbenza, but Ramadan Sobhi could be denied a reunion with the club he left in a £5.7m deal during the summer by a knee injury sustained in training.
Wagner added: “Since I arrived we have used rotation if at all possible or necessary. Everyone knows that.
“We have three games in a week and it could be a good idea to do this again. How we do it, this is to be decided on Tuesday morning.
“The truth is we had 23 players training on Friday, all fit and all healthy and all hungry. Everyone was wanting to shine and show how good he is.
“But Ramadan Sobhi got a knock on his knee. He finished training early, but even he can be available. This means I have to think about it. As I said, I do love fresh legs in competitions.”
Jonas Lossl will start in goal after coming off the bench to replace the injured Ben Hamer against Cardiff, but Wagner does not expect Town old boy Ince to be in opposition tonight.
“I heard from the players who speak to Tom (Ince) that he has a serious hamstring injury,” added the Terriers’ chief.