The young Magpies will bid to lift the trophy for the first time since 2018 and face the Aristocrats who compete in the Northern League Division Two - the tenth tier of English football. Kick-off is set at 7.30pm (BST).
United's youngsters reached the final in 2022 before suffering a narrow 3-2 defeat against Blyth Spartans at St. James' Park.
Current holders, Morpeth Town, and Blyth Spartans have both received byes to the quarter-final stages.
Northumberland Senior Cup first round draw:
Newcastle Benfield vs Heaton Stannington
Ashington vs Newcastle University
Newcastle United Under-21s vs Newcastle Blue Star
Bedlington Terriers vs Prudhoe YC Seniors
Whitley Bay vs Blyth Town
North Shields vs West Allotment Celtic