The tournament is split into eight groups of four teams, with United's second-string aiming to qualify for the knockout stages as one of the top two sides in Group G.
The young Magpies enjoyed a memorable run to the Premier League Cup final in 2019, beating the likes of Reading, Derby County and Leeds United, before suffering a narrow 1-0 defeat against Everton at Goodison Park.
Birmingham are the only side which compete in the same division as United's youngsters, with the Blues also plying their trade in the second tier of the Premier League 2.
Newcastle's second-string will face each side home and away as they bid to seal their place in the last 16 for the fourth successive season.
Premier League Cup fixture list:
Watford (A) - Monday, 6th September (kick-off 6pm BST)
Birmingham City (H) - Monday, 11th October (kick-off 7pm BST)
Huddersfield Town (H) - Monday, 17th November (kick-off 7pm GMT)
Watford (H) - Friday, 10th December (kick-off 6pm GMT)
Birmingham City (A) - Friday, 21st January (kick-off 7pm GMT)
Huddersfield Town (A) - Monday, 14th February (kick-off 7pm GMT)