The 22-year-old former Rotherham lock will partner Alex Brown in the second row - eager to stake his claim for even more regular rugby as part of Dean Ryan's side.
Pendlebury's elevation is the major change to the regular Premiership starting line-up for Gloucester's trip to High Wycombe and a venue where they have never won in the Premiership.
He is one of five changes to the starting XV that dismantled Toulon 66-5 in the European Challenge Cup last weekend.
Olly Morgan returns at full-back in place of Jon Goodridge, Mark Foster switches wings to accommodate James Bailey, Patrice Collazo comes in at loosehead for Nick Wood, Phil Vickery is back at tighthead and Andy Hazell returns on the openside in place of Jake Boer.
But Pendlebury, who has served his time in Gloucester's Guinness A League side, told www.gloucesterrugby.co.uk "My aim has been to play senior rugby this season and now I want to make a contribution - I don't want to be carried by the rest of the lads.
"The last few weeks have gone pretty well and I have been pleased with how it's gone but Monday's game will be a different test entirely.
"I always thought I could get a chance and now I just want to take it. We know it will be tough because Wasps are an outstanding side but we are all really excited about the challenge we face.
"It is my first start for the club in the Premiership and it probably couldn't come in a bigger game. It's a massive test for everyone. We have been building up for this game in our last two games against Toulon and we will be right up for it."
Pendlebury has Premiership experience with his former club Rotherham but signed a two-year deal with Gloucester in the summer having impressed last season on a trial basis.
He has been a regular in the Guinness A League side this season and made his competitive debut against Toulon in France earlier this month.
Head coach Ryan has otherwise kept the changes to a minimum. He has recalled Morgan to the full-back position and he will make his fifth appearance of the season.
Both Collazo and Vickery return in the front row having been rested last weekend, while Hazell also gets the call at openside in place of Jake Boer.
The only real alteration comes on the wing where James Bailey will make only his second Premiership appearance of the season following his try-scoring effort against Saracens last month in place of Rob Thirlby.
The only major injury concern centred around number eight James Forrester but his damaged ribs have recovered enough to allow him to take his position on the back of the scrum.
"We were on a bit of a role before the autumn internationals and now we are back in the Premiership we have to rediscover that form," Ryan said.
"We want to challenge for the right to win at places like Wasps. They have been one of the form teams in the Premiership for a long time and they are a very tough side to beat.
"But I don't want to talk about records. We have a job to do this weekend - that's all that matters."
GLOUCESTER (v Wasps, Monday, December 26, away, 3pm): Olly Morgan; Mark Foster, James Simpson-Daniel, Mike Tindall, James Bailey; Ludovic Mercier, Peter Richards; Patrice Collazo, Mefin Davies, Phil Vickery (Capt), Jonathan Pendlebury, Alex Brown, Adam Balding, Andy Hazell, James Forrester. Reps: Rob Elloway, Gary Powell, Adam Eustace, Jake Boer, Haydn Thomas, Terry Fanolua, Brad Davies.
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