The young Magpies are one of 16 Category One academies invited to enter an under-21 side into this season's competition and were drawn alongside Huddersfield Town, Mansfield Town and Harrogate Town in Group F of the Northern Section.
United's second-string will travel to the Accu Stadium to face Huddersfield on Tuesday, 2 September (kick-off 7.45pm BST) before taking on Mansfield - who claimed a 3-0 win against the young Magpies in last season's competition - at the One Call Stadium on Wednesday, 15 October (kick-off 7.45pm BST).
United's youngsters will then face an away trip to Harrogate Town, who Newcastle's second-string faced in the 2021/22 competition, at the Exercise Stadium on Tuesday, 11 November (kick-off 7.45pm GMT).
Last term, Newcastle were unable to progress from a group featuring Bradford City, Rotherham United and Mansfield but in 2018/19, they won all three of their group games before beating Macclesfield Town via penalties at St. James' Park to set up a last-16 tie against Sunderland, who came out on top at the Stadium of Light in front of a crowd of over 16,000 spectators.