After wins against Stoke and Tottenham, the Reds face a North-East double header stretched over a long weekend with the Magpies at Moss Lane before a trip to Sunderland on Monday night.
Angelo Henriquez is included in a Reds squad for the first time and is set to make a debut appearance since arriving from Universidad de Chile.
With Scott Wootton and Michael Keane playing for 90 minutes against the Tynesiders' senior team on Wednesday, and in contention for Sir Alex's squad against Spurs on Saturday, there is a need for a defensive reshuffle.
Larnell Cole could play at full-back while Tom Thorpe looks certain to start in the middle of the defence. As expected, Italians Davide Petrucci and Federico Macheda feature in an exciting line-up.
Newcastle sit above United in the table in second place, albeit having played two games more, and 17-year-old Adam Campbell, already being dubbed the 'new Alan Shearer' in some quarters, will be one to watch with four goals in four games after a fruitful Milk Cup campaign in the summer. Bradden Inman has also been amongst the goals while Romain Amalfitano and Mehdi Abeid have been named in the squad.
The Reds are aiming for a hat-trick of wins against the Sports Direct Arena outfit after the Under-18s and first team both triumphed over the course of the last week and, last season, a thrilling 6-3 success on Tyneside clinched the Reserves title.