The Ukrainian champions have not played at their Donbas Arena home in Donetsk since 2014 and have staged European home games in Poland, Germany and Slovenia since Russia launched a full-scale invasion of Ukraine in 2022.
In a bid to reduce travel commitments, Shakhtar were keen to host their Champions League home fixtures in London this season and considered Fulham and Brentford as potential venues.
London also has a sizeable Ukrainian refugee population, and 29,144 people turned out as Shakhtar came from behind to beat AEK Athens, with Mudryk and former Chelsea striker Andriy Shevchenko - now the president of the Ukrainian Football Association - both in the stands.
Mudryk, who is currently on a season-long loan at London rivals Tottenham, has not played a competitive game for Chelsea in nearly two years.
The 25-year-old was cleared to play again with immediate effect this summer after he resolved his anti-doping disciplinary proceedings with the Football Association (FA), and he headed to Spurs in a shock move on Deadline Day to reunite with ex-Shakhtar boss Roberto De Zerbi, alongside centre-back Tosin Adarabioyo.
Mudryk has endured a frustrating start to life in north London and has been out of action since the beginning of September with an ankle ligament injury suffered in training just days after his debut off the bench at Nottingham Forest.
He will be ineligible to face his parent club when Spurs travel to Stamford Bridge next Saturday, even if fit.
Shakhtar, meanwhile, hope to average 30,000 fans across their four matches at Stamford Bridge, which has a capacity of 40,044, with fixtures against Sporting, Fenerbahce and Real Madrid still to come.