The Scotland international midfielder made his first appearance for United as a second-half substitute against Galatasaray last week since his chronic bowel condition left his football career hanging in the balance.
Now he is set to make his first start since November last year after spending the end of last season helping to coach United's reserve side as he battled the illness before working during the summer to make his comeback.
Fletcher, 28, has had to change his diet and adapt his lifestyle to overcome the ulcerative colitis condition and United manager Alex Ferguson is delighted to be able to include him in his starting line-up on Wednesday as he prepares to make a host of changes from their 2-1 win over Liverpool on Sunday.
If the Scot comes through the game unscathed he could be in line for his Premier League return against Tottenham on Saturday.
Ferguson said: "Fletcher will certainly play against Newcastle and that is the perfect game for him to start back. Then we have the game against Tottenham and he could be involved in that.
"It depends on how he does on Wednesday. It will be his first 90 minutes since 10 months out. It's a big one for him. He is handling the condition at the moment, as we saw the other night he is looking fine.
"It is a matter of hoping the condition stays dormant and he is handling his diet well. Hopefully he gets that break."
Ashley Young will miss out as he is out until October with a knee injury while Wayne Rooney is still not fit following the nasty cut he received on his thigh last month against Fulham.
Ferguson will opt to make a number of changes for the League Cup as he usually does in the early stages and Alexander Buttner, Anderson and Tom Cleverley could all feature having not played a part in the Liverpool game despite being on the bench.
Meanwhile, United defender Rio Ferdinand expressed his relief at getting the game against Liverpool out of the way after United stuttered to victory over 10 men on an emotional afternoon when Hillsborough was remembered.
He said: "With the occasion and the emotions involved, we just wanted to come here, get the job done and get out with the three points. We have done that so we are well pleased.
"You can get really involved and sometimes the emotion of the occasion can affect you, but they dealt with it fantastically."
Newcastle are likely to field a strong side with Fabricio Coloccini and Cheick Tiote set to start to get some more minutes under their belt while Shola Ameobi, Dan Gosling and Sylvain Marveaux could also feature.
Coloccini has not played since Newcastle's draw with Aston Villa on September 2 while Tiote made just his second appearance of the season in Newcastle's win over Norwich on Sunday.
The Magpies have not won at Old Trafford since 1972. However, manager Alan Pardew is going to give the competition a real go despite knowing it will be a tough test against Ferguson's side even if the hosts field a weakened side.
Pardew said: "Of course you want to enjoy going there. We are going to have make sure we can get game time out of the players that will need it.
"Colo could play, Cheick definitely needs a game, he was rusty (against Norwich), so I will have a word with the staff and hopefully we'll get a result there."
Goalkeeper Tim Krul will definitely miss out with Pardew mulling over the decision on whether to field veteran Steve Harper or Rob Elliot, who played in their Europa League tie with Maritimo last week.
Source: AFP
Source: AFP