Fletcher, 28, is on the comeback trail as he tries to combat a chronic bowel problem and came on for the final 11 minutes in the Champions League win over Galatasaray last week.
He was also in the squad for the Premier League hammering of Wigan the previous Saturday.
The Scotland skipper has suffered the problem since March 2011, although it was not made public until December after the Dalkeith-born midfielder gave up trying to battle through.
In the end it was decided he needed an extended rest from the game, during which time he has been doing some coaching with United's junior teams.
Fletcher has stepped up his recovery programme this season though and also featured in a reserve match at Stalybridge Celtic recently.
"I am looking at the Newcastle cup tie as a starting point for him because we alter the make-up of the side for these games," United manager Ferguson said at the start of last week.
Wayne Rooney, who has not played for a month after suffering a severely gashed thigh against Fulham, is could also return against the Magpies.
Rooney's leg was badly cut in an accidental clash with Fulham forward Hugo Rodallega at Old Trafford on August 25 but he could play against Newcastle on Wednesday or against Tottenham Hotspur in the Premier League on Saturday.
"He is not far away," Ferguson said. "He's doing a lot of great training and has been working hard."
New-boy Angelo Henriquez - who is not available for Champions League games as United did not receive international clearance in time for him to be registered - is available for the Red Devils, whilst Nick Powell and Alex Buttner are also amongst those set to make the starting line-up.