The Ukrainian champions began the league phase with a 1-1 draw away to PSV Eindhoven last month and open their Stamford Bridge account when they host AEK Athens of Greece on Wednesday night.
Due to conflict in the Donbas region, Shakhtar have not been able to play at their home ground, the Donbas Arena, since 2014.
Though they play domestic games in the western Ukrainian city of Lviv, they have spent time playing ‘at home’ in Germany, Poland and Slovenia in recent seasons in Europe.
Now comes the turn of England to play host to the 16-time winners of the Ukrainian Premier League.
Brentford’s Gtech Community Stadium and Fulham’s Craven Cottage were considered as potential options, but Stamford Bridge, the home of Chelsea, was eventually chosen as Shakhtar’s home from home in the Champions League this season.
Under the lights: Shakhtar Donetsk will play Champions League matches at Chelsea’s Stamford Bridge
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The club’s chief executive Sergei Palkin explained: “We decided: let's move to England. There are a lot of Ukrainian refugees and a lot of Ukrainians living here.
“London is the football capital of the world. It's the biggest marketplace for players. For our young players to play at this level in a legendary stadium like Stamford Bridge provides extra motivation and can bring positive results.
“I first contacted [Chelsea co-owner] Behdad Eghbali and said: ‘What do you think about this idea – playing Champions League matches in your stadium?’
“The reaction was positive. Step by step, it became a reality. Chelsea were very professional.”
Shakhtar’s Champions League league phase games at Stamford Bridge see them face AEK on Wednesday, Portuguese side Sporting on November 3, Fenerbahce on November 25 and Real Madrid on January 27.