The victors of this tie will meet either Leyton Orient or Tottenham Hotspur in the fourth round, with those two sides set to face off on Tuesday.
In gameweek two of the new Premier League season, Chelsea welcomed Liverpool to a ground where they were unbeaten in their last 13 league matches against the reigning champions - winning seven and drawing six in that run.
However, the Reds ran out comfortable winners against Frank Lampard's side thanks to a quickfire double from Sadio Mane, and Chelsea have little time to dwell on that defeat as they bid to lift the EFL Cup for the first time since the 2014-15 campaign.
The Blues last reached the final as recently as the 2018-19 season, where they ultimately fell to defeat against Manchester City in a penalty shootout, but Chelsea were knocked out by City's bitter rivals Manchester United in round four last season.
The five-time EFL Cup winners have not failed to make it past the third round since Newcastle United enjoyed a 4-3 victory at Stamford Bridge in the 2010-11 season, and Chelsea will no doubt feel confident about their chances of advancing against a Barnsley side enduring a mediocre start to the new Championship campaign.
Barnsley just about managed to stave off relegation from the second tier last season, but the Tykes have already lost as many matches this season as they did in their final nine of the 2019-20 campaign.
Gerhard Struber's men have opened their new campaign with defeats to Luton Town and most recently Reading, and are yet to register a goal in the new league season.
However, Struber's side already have two EFL Cup victories to their name as they overcame fellow Championship sides Nottingham Forest and Middlesbrough to set up a clash with Chelsea, and Barnsley have already bettered their last two runs in this tournament where they were knocked out at the first hurdle.
The Tykes faced off against Premier League opposition from the capital when they last reached round three in the 2017-18 campaign, but a Dele Alli goal saw Tottenham Hotspur overcome Barnsley in that game.
Should Struber's side pull off an unexpected victory against the Blues in midweek, it will mark the first time that Barnsley have advanced past round three since the 2009-10 campaign, where they were ultimately knocked out by Manchester United in the quarter-finals.
Barnsley and Chelsea have not met each other since the 2007-08 FA Cup campaign, where the Tykes famously prevailed 1-0 against the Blues to reach the semi-finals.
Chelsea form (all competitions): WL
Barnsley EFL Cup form: WW
Barnsley form (all competitions): WLWL
Andreas Christensen was given his marching orders for hauling down Mane at the end of the first half, and the defender will play no part in this one.
As far as any potential changes are concerned, Fikayo Tomori and Callum Hudson-Odoi will both be holding out for starting roles, but the game will come too soon for Christian Pulisic to return or for Hakim Ziyech to make his competitive debut.
However, Lampard has revealed that Ben Chilwell and Thiago Silva are in the squad for Wednesday, and both defenders have a chance of stepping out onto the Stamford Bridge turf for the first time in a Chelsea shirt.
While Chelsea had one defender in Christensen sent off in their last league match, two of Barnsley's centre-backs were made to take the walk of shame as Mads Andersen and Michal Helik both saw red against Reading, while Bambo Diaby remains suspended.
Other than that, Struber has a fully-fit squad to pick from as Barnsley look to defy the odds and knock out the five-time winners.
Chelsea possible starting lineup:
Caballero; Azpilicueta, Rudiger, Tomori, Emerson; Jorginho, Barkley, Loftus-Cheek; Havertz, Abraham, Hudson-Odoi
Barnsley possible starting lineup:
Walton; Sollbauer, Halme, Omar; Ludewig, Ritzmaier, Mowatt, Williams; Thomas, Schmidt, Frieser
We say: Chelsea 4-0 Barnsley
A clash with an out-of-sorts Barnsley side represents the perfect opportunity for Chelsea to boost their confidence following that dismal defeat to Liverpool. The visitors will put up a fight but are not going to prove any match for the Blues, so we are expecting Lampard's men to record a straightforward victory and book their spot in the fourth round.