There are 41 places between the sides in the English football pyramid, as the Red Devils will look for an easy passage into the fourth round.
In what is a dream draw for the League One side, it will be the first meeting between the sides in 15 years, as the Tykes will look to make the most of their big day out.
Here, Sports Mole takes an in-depth look at the head-to-head record and previous meetings between Man United and Barnsley.
Head-to-head record
Previous meetings: 38
Man Utd wins: 22
Draws: 11
Barnsley wins: 5
With Manchester United and Barnsley only sharing the same division once since World War Two, it is no surprise that the clubs have only met six times since 1938.
The most recent of those clashes came in this competition back in 2009, when the two faced off at Oakwell in the last 16.
Danny Welbeck and Michael Owen scored the goals as Sir Alex Ferguson's side won 2-0, despite a Gary Neville red card, and they would go on to win the competition that season, beating Aston Villa at Wembley.
Neville was also in the squad when Barnsley caused a huge shock by knocking the Red Devils out of the FA Cup in 1998, forcing a replay after drawing 1-1 at Old Trafford, and then winning 3-2 on home soil.
John Hendrie's first-half double was the catalyst for the win, and even though Andy Cole and Teddy Sheringham scored after the break, United were eliminated.
That was revenge for a 7-0 hammering that Man United had inflicted on the Tykes just a few months earlier in their only season as a Premier League club, with Cole scoring a hat-trick.
Cole and Sheringham netted once again on the final day of that season in a 2-0 win at Oakwell, as Barnsley were relegated from the top flight, and have still never returned.
The only other post-war fixture was in 1964, when Denis Law and George Best were among the goals in a convincing 4-0 Man United victory in the FA Cup.
All other 31 meetings came in the old Division Two between 1898 and 1938, and the first two of those were when United were still referred to as Newton Heath.
The most intriguing set of games in that period were in 1923, as both league games that season were played on consecutive days, which just so happened to be Christmas Day and Boxing Day, with Barnsley winning both.
Last 20 meetings
Oct 27, 2009: Barnsley 0-2 Man Utd (EFL Cup)
May 10, 1998: Barnsley 0-2 Man Utd (Premier League)
Feb 25, 1998: Barnsley 3-2 Man Utd (FA Cup replay)
Feb 14, 1998: Man Utd 1-1 Barnsley (FA Cup)
Oct 25, 1997: Man Utd 7-0 Barnsley (Premier League)
Feb 15, 1964: Barnsley 0-4 Man Utd (FA Cup)
Feb 02, 1938: Barnsley 2-2 Man Utd (Division Two)
Jan 26, 1938: Man Utd 1-0 Barnsley (FA Cup replay)
Jan 22, 1938: Barnsley 2-2 Man Utd (FA Cup)
Sep 11, 1937: Man Utd 4-1 Barnsley (Division Two)
Jan 01, 1936: Barnsley 0-3 Man Utd (Division Two)
Dec 26, 1935: Man Utd 1-1 Barnsley (Division Two)
Jan 19, 1935: Barnsley 0-2 Man Utd (Division Two)
Sep 08, 1934: Man Utd 4-1 Barnsley (Division Two)
Feb 27, 1932: Man Utd 3-0 Barnsley (Division Two)
Oct 17, 1931: Barnsley 0-0 Man Utd (Division Two)
May 02, 1925: Barnsley 0-0 Man Utd (Division Two)
Sep 08, 1924: Man Utd 1-0 Barnsley (Division Two)
Dec 26, 1923: Barnsley 1-0 Man Utd (Division Two)
Dec 25, 1923: Man Utd 1-2 Barnsley (Division Two)
Previous EFL Cup meeting
Oct 27, 2009: Barnsley 0-2 Man Utd
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