And, for a number of long-serving players, that will mean the end of their careers at the 14th-placed club, which is safe from relegation with two games to go following a remarkable mid-season turnaround under Eddie Howe.
At least a dozen players are expected to leave this summer, and some of those facing uncertain futures at St James’s Park will be involved against Arsenal on Monday night.
Those that aren’t will take part in a lap of appreciation after the Premier League game, the club’s final home fixture this season.
"It's difficult to speak about individuals, but I'm sure for some of my players, it may well be an emotional experience,” said Howe, who left Ciaran Clark out of his 25-man Premier League squad once the January window closed along with the injured Isaac Hayden and Jamal Lewis.
“I'm very much in the mindset that we have to be very appreciative of everybody's efforts to our success this season in terms of the position we were in to where we are now.
“Everyone’s played their part in that, whether they have participated on the pitch or not.
"I look at Ciaran Clark, Isaac Hayden and Jamal Lewis, who were not in the 25-man squad, but their attitude to that disappointment has been incredible.
“They're still training with the group and they've not been negative or disappointed for a moment.
“It's important that I highlight that, because we haven't achieved anything as individuals. It's been the collective group that's done it – and full credit to everyone."
Clark is set to leave in the summer for first-team football, while Hayden and Lewis could also leave.
The futures of Federico Fernandez, Karl Darlow, Matt Ritchie and Dwight Gayle also look to lie elsewhere after fringe roles this season.
And Howe – who hopes to further strengthen his squad in the summer window – admits he has some “difficult decisions” to make on individuals, though he won’t be drawn into discussing the futures of individuals before the end of the campaign.
“There's some difficult decisions to make, and, naturally, when you look at the squad, we’re top heavy,” said United’s head coach.
“We have a lot of players, players who missed out on the 25.
“As I said before, we'll make decisions on every individual, we'll try to do it in the right way. No decisions have been made yet, get the games out the way first and then we'll make them.”
Meanwhile, one player who is set to stay at Newcastle is Sean Longstaff, who is “very close” to signing a new deal.
The 24-year-old midfielder is out of contract at the end of the season, and Howe said: "I expect a positive resolution for Sean, yeah. Fingers crossed.
“It’s very close to being done. I’m not actually in charge of that, but fingers crossed we can get it over the line.”
United’s final game of the season is a May 22 fixture against relegation-threatened Burnley at Turf Moor.