Pep Guardiola's side won the competition back in February through a penalty shootout victory against Chelsea and will be determined to become the first side since Liverpool in 1983 to win the competition three times in a row.
However, City come up against a spirited Preston side currently enjoying a strong spell of form in the Championship.
Match preview© Reuters
Following a period in the wilderness of League One between 2011 and 2015, Preston have enjoyed much more stability in the Championship over recent years, with their lowest finish since returning to the second division coming when they ended last season in 14th place - still 21 points clear of safety.
Under the leadership of manager Alex Neil, who joined the club in 2017, The Lilywhites have enjoyed an excellent start to the new campaign, winning five of their opening eight Championship games - a run which has taken them to third in the table - alongside winning ties against Hull City and Stoke City to set up this clash with another City at Deepdale.
A deeply energetic, organised unit, Preston are yet to lose at home this season and their win at Birmingham last weekend was an example of a team which, although not blessed with swathes of talent, possesses an inherent steeliness emblematic of so many Championship sides.
While you would have to go all the way back to 2001 for when the two sides last met, Preston can take heart from recent cup performances against Manchester United and Arsenal in 2015 and 2017 respectively, taking the lead in both of those games and sending shockwaves across the footballing world amid the possibility of an upset, only to lose each game late on as defenders started to tire.
In his team talk ahead of the game, Neil may well reference Norwich City, the club he managed before coming to Deepdale, as an example of what can happen when City's acute passing is put under a heavy press and every player religiously sticks to their game-plan for a full 90 minutes. Nobody expected that 3-2 win for the Canaries, but the sheer organisation of each player was enough to give Daniel Farke's side a deserved win - something Neil will insist that his players are capable of doing as well.
What Neil may omit from his team talk, however, is the fact that since the defeat at Carrow Road, City have played two games and scored 11 unanswered goals, including a 8-0 win over Watford during which the hosts scored five times in under 18 minutes.
Moreover, City have acquired recent supremacy in the EFL Cup, winning the competition on four occasions over the last six years, with last year's run including a 10-0 aggregate victory over Burton Albion whilst conceding just once on their route to victory at Wembley.
Giant killings are always possible even against a side with City's quality, as demonstrated in the FA Cup fifth round in 2018, when Will Grigg scored the only goal of the game, but it would take something herculean for Preston to keep City's attack out for a full 90 minutes.
It is the sheer pace and precision of City's passing, combined with the impeccable skill at close quarters from players like Bernardo Silva, which serves to wear down a Championship team in a much more brutal and abrupt manner than normal, to the point where, on the 80th minute mark, players are usually listlessly snapping at the heels of City's players, the game reduced to something of a training session.
Even if Preston do, by some miracle, find themselves in a winning position after 70 minutes, they then face the extra task of simultaneously battling fatigue and Guardiola's big guns, such as Kevin De Bruyne and Sergio Aguero, being brought on from the bench to provide a fresh assault on the back four.
Against a team which has scored 27 goals from its opening seven games this season, Preston's primary task will be to stem City's flow, to somehow block their route to goal. If they can manage that whilst maintaining perfect energy levels, the Championship side could shock the football world.
Recent Preston North End form: WWDWW
Recent Manchester City form: WWLWW
Team News© Reuters
Preston will be without captain and central defender Tom Clarke, who has been an indispensable figure for the Championship side, while striker Louis Moult is the club's only long-term absentee as he continues to recover from an ACL injury.
For City, Phil Foden ought to make a return to the side having missed the last pair of matchday squads due to a stomach virus.
Preston North End possible starting lineup:
Rudd; Fisher, Bauer, Davies, Raverty; Browne, Pearson; Maguire, Johnson, Harrop; Barkhuizen
Manchester City possible starting lineup:
Bravo; Cancelo, Garcia, Fernandinho, Mendy; Gundogan, Rodri, Foden; Sterling, Jesus, Bernardo
We say: Preston North End 1-4 Manchester City
Preston will fly out of the blocks and should give a second-string City side, whose defence is far from perfect, a few problems early on, but the sheer class of the Premier League champions, as it does on 99 out of 100 occasions, will ultimately shine through the longer the game goes on.
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