The Magpies are one of 16 Category One academies who are taking part in this term’s competition, which will commence in September.
And United, who will be led by under-21s lead coach Ben Dawson, will learn their opponents when the group stage draw is made live on Sky Sports News from 2:30pm (BST) on Thursday, 27th June.
All 64 teams enter from Round One and are to be split into 16 regional groups of four teams, with eight clubs in the Northern region and eight in the Southern region.
The 16 invited under-21 teams will be placed into their respective Northern and Southern regional groups, with the 48 EFL Clubs placed into pre-determined groups prior to the draw.
Last season, Newcastle were unable to progress from a group featuring Wrexham, Port Vale and Crewe Alexandra but, in 2018/19, the young Magpies won all three of their group games against Notts County, Doncaster Rovers and Grimsby Town to top the group.
After seeing off Macclesfield Town on penalties at St. James’ Park, Newcastle's second-string exited at the round of 16 stage following a 4-0 defeat against Sunderland at the Stadium of Light.
Along with Newcastle, the 15 other invited Category One academy clubs are Arsenal, Aston Villa, Brighton & Hove Albion, Chelsea, Crystal Palace, Everton, Fulham, Leicester City and Liverpool.
Manchester City, Manchester United, Nottingham Forest, Tottenham Hotspur, West Ham United and Wolverhampton Wanderers complete the list of invited under-21 sides.