However, the Premier League champions did not have the best preparation for their Group C match after suffering a shock 3-2 defeat at Norwich City on Saturday.
It was the Sky Blues' first defeat in the English top flight since January, and Pep Guardiola's side will need to bounce back fast if they are to make a winning start to their European campaign this season against Shakhtar.
Here are all the details for the fixture:
Date: Wednesday, September 18
Time: 8 p.m. BST, 3 p.m. ET
TV Info: BT Sport 3 (UK)
Odds (courtesy of Caesars): Shakhtar 87-10, City 31-100, Draw 9-2
City against Shakhtar is starting to become an annual tradition in the Champions League.
This is the third consecutive season in which they have been placed in the same group, and City have come out on top more often than not.
Last term, the Sky Blues beat the Ukrainian outfit 6-0 at home and 3-0 away.
The season before, Shakhtar lost 2-0 in Manchester but claimed a 2-1 win at the Metalist Stadium.
Guardiola will not allow his side to be complacent, especially given City have arguably underperformed in Europe's elite competition during his tenure despite their record-breaking heroics domestically:
Football on BT Sport @btsportfootball
Pep Guardiola hasn't gone past the quarter-final stage in the Champions League in his three seasons in charge of Man City: 2018/19: Quarter-finals ❌ 2017/18: Quarter-finals ❌ 2016/17: Last-16 ❌ Tottenham, Liverpool and Monaco knocking them out. https://t.co/5v9AiZn5PP
Statman Dave @StatmanDave
In their #UCL campaign, Man City beat: 🇺🇦 Shakhtar Donetsk (1st in Ukrainian Premier League) 🇩🇪 Hoffenheim (6th in Bundesliga) 🇩🇪 Schalke (15th in Bundesliga) They failed to beat: 🏴 Spurs (3rd in Premier League) 🇫🇷 Lyon (3rd in Ligue 1) Another subpar campaign. 🤔🤔🤔 https://t.co/t368C2Hn28
Shakhtar, who sit atop the Ukrainian Premier League table, can take confidence from Norwich's remarkable victory.
City are vulnerable in defence with Aymeric Laporte sidelined by a serious knee injury:
It is understandable Shakhtar are underdogs for Wednesday's clash even though they are at home as they do not boast anything like the attacking talent in City's squad.
However, if the hosts can get an early goal against the Premier League champions, they could claim a shock victory in the first round of group games.