Centre Jamie Noon is not available due to England training ahead of the autumn Tests, meaning a debut for summer signing James Hoyle on the left wing as Mathew Tait pushes infield one place to outside centre.
Andy Buist replaces Geoff Parling at lock after he picked up a calf injury in Sunday's 26-11 win at Border Reivers, while in the front row Micky Ward replaces loose head Grant Anderson and Robbie Morris comes in on the tight head side for Tino Paoletti.
The only other change is at scrum half where James Grindal replaces Hall Charlton, who suffered damage to the medial collateral ligament of his left knee at Borders.
On the bench England Under-21s scrum half Lee Dickson is drafted in, while Academy No.8 Jason Smithson could make his senior club debut after becoming the top try scorer in the Guinness A League with six touch downs in seven outings.
Fit-again Joe Shaw could make his first appearance of the season after recovering from a long-term ankle injury, one ironically picked up at Kingsholm in the early stages of last season.
Hooker Andy Long has been given until match-day to prove his fitness after a groin strain and could be among the replacements, with Grant Anderson covering hooking duties on the bench should Long not make kick-off while Ben Woods also returns to the match-day 22 after shoulder trouble.
With Kingsholm having been an impenetrable fortress for the Falcons in recent seasons, director of rugby, Rob Andrew, said in the build-up to Saturday's showdown: "We've won at Franklin's Gardens this season, were robbed of a win at Welford Road and I suppose Kingsholm is bogey ground No.3.
"At Leicester we laid a few ghosts to rest in claiming a moral victory in what should have been an actual victory on a few counts, and Kingsholm is the only other ground where we haven't been successful since we won the league in 1998. We've been closer at Kingsholm than we have at the other two down the years, but the victory has eluded us, so Saturday is a great chance to try and take that record away from them."
Having traditionally endured a tough time on the road, the Falcons' play away from Kingston Park thus far has been encouraging, with Andrew stating: "Our away form has been much more consistent than any other year I can remember from the recent past, with wins at Northampton and Borders, plus good performances at Sale, Leicester and Llanelli.
"October has been a good month for us all round if we look at it as a whole, but the unfortunate thing is that only one of those games was in the Premiership. This next month is different in that all four games are in the league, and all four coincide with internationals, which poses different problems and issues.
"We have a lot of injuries and a couple of people away with their countries, but we feel we're strong enough to ride it out and put some results together in the Premiership with the players we've assembled.
"When you look at the list of those missing we are without some strong players such as Andy Long, Stuart Grimes, Phil Dowson, Andy Perry, Jamie Noon, Colin Charvis, Anthony Elliott, Geoff Parling, Hall Charlton and Mark Mayerhofler, so it's a big test of our strength in depth.
"That's a heck of a list of absentees, but when you look at the team sheet and see the XV we are putting out for Saturday, it's a talented team."
There is a new captain for the weekend, as Andrew explained: "With Charv being with Wales this week Jonny will captain the team, and even when Colin is around, Jonny has a tendency to be very vocal anyway with the players, so that won't change things at all really and it's just a formality."
With former Sale Shark James Hoyle set for his competitive Falcons debut after just one start in the pre-season match against Toyota in Japan, Andrew said: "James hasn't started a Premiership game yet, but his form in the Development Team has been excellent.
"He's been very close to getting his chance for a few weeks, and it's only been the form of Elliott, May and Tait which has prevented him from being in the mix. He has a lot of pace, but more importantly he's also a very good footballer with excellent skills and vision. He is very much in the mould of the young backs we're trying to bring through.
"He was Mathew Tait's equivalent the year before Taity actually came through with the England Schools team, and he was arguably the best English Schoolboy player of his era three years ago.
"About two seasons ago we tried to sign him but he went to Sale, and he just got lost there a bit because they never really gave him the chance due to having the likes of Cueto, Hanley and Robinson there at the time. He didn't develop there as he should have done, but since he's come here he has looked very sharp and has all the skills needed, such as being an extremely elusive runner with very deceptive pace."
Another young player making great strides has been 20-year-old Toby Flood, who scored a well-worked team try at Borders last Sunday in what was his first ever start at inside centre.
"One of my gain goals this season from an individual development point of view is to get Toby as much experience as I can at 10 or 12, as we did with Jonny when he first came to us," said Andrew.
"That gives us more options in the key midfield area, which is very tough to operate in at the top level. That is one of the hardest areas on the field because not only do you have to be a decision maker, but you have to be as tough as a flanker in all respects due to the demands of the modern game.
"Toby has all the characteristics, good hands, great kicking and pace, but he's a tough kid as well. If we can develop him along the lines that we did with Jonny, and he has all the attributes to do so, then he will be a top, top player.. He was by far the man of the match against Borders last week, and the pressure just doesn't seem to faze him at all."
Away from club matters, with much attention drawing in on the imminent autumn internationals, Andrew was quick to praise one of Saturday's absentees, England centre Jamie Noon.
"He's been retained in the 22 which was announced today, and he has to start for my money because he's been the best centre in England this season by an absolute mile," he said.
"He's been effective in every single game he's played for us, and I just hope that now England stick with him and give him a good run in the side, because he is a man who could go on to win a lot of caps with the qualities he has as an international player at the very top level."
Newcastle Falcons team to face Gloucester:
15 Matthew Burke
14 Tom May
13 Mathew Tait
12 Toby Flood
11 James Hoyle
10 Jonny Wilkinson (captain)
9 James Grindal
1 Micky Ward
2 Matt Thompson
3 Robbie Morris
4 Luke Gross
5 Andy Buist
6 Mike McCarthy
7 Cory Harris
8 Owen Finegan