The Magpies are one of 16 Premier League academy sides invited to compete against teams from League One and League Two in the competition, with the initial group stage draw divided into Northern and Southern sections.
United's youngsters have been confirmed in Group B of the Northern section, with newly-promoted Wrexham and Crewe Alexandra the two fourth tier sides they will face, while Port Vale are currently in the third tier.
Newcastle have previously faced both the Alex and the Valiants in the competition. In the 2017/18 campaign - the Magpies' first season taking part - a 2-1 victory over Crewe at Gresty Road was followed by a 1-0 defeat at Vale Park as United exited at the group stage.
Port Vale were also drawn in Newcastle's group in 2019/20, with Elliot Anderson netting during a 2-1 reverse away from home, while Crewe later held the young Magpies to a goalless draw in 2020/21.
Confirmed fixture dates and ticket details will be announced in due course.