The Armenia star had been ever-present in the Premier League until the visit of Rafa Benitez's men to Old Trafford, a game for which he did not even make the matchday squad.
Mkhitaryan started the season in fine form but has been struggling to influence matches in recent weeks, particularly the 0-0 draw with Liverpool at Anfield and defeats to Huddersfield Town and Chelsea.
His omission from the Newcastle game prompted speculation he could be set to endure another prolonged spell out of the team - the former Borussia Dortmund man having spent weeks out of Mourinho's plans in the early months of last season before forcing his way back into the team at the end of November.
Mourinho, however, believes there is unfair scrutiny whenever he leaves a prominent player out of his starting line-up.
"It's a bit frustrating for me, the fact that there is always a question about some player who is not playing or in the best of his form," the United manager told a news conference ahead of Wednesday's Champions League clash with Basel.
"No questions about Martial, no questions about Chris Smalling, it's always about players in a certain moment, match, period who didn't play or was not my option.
"The story is always the thing. In some positions where you don't have injuries, you don't have options, and always the same players are playing.
"In the midfield it was the same, a bit. No [Michael] Carrick, [Paul] Pogba, [Marouane] Fellaini and every match was [Ander] Herrera and [Nemanja] Matic and the kid [Scott] McTominay had his opportunities to play.
"In this moment, we have Pogba, Fellaini, Matic, McTominay; next week, I can imagine you will ask why is this player not playing.
"I decided to play Rashford and Martial together. The question for many weeks was 'why don't they play together?'. Now, it's 'why isn't Mkhitaryan playing?'. The answer is very simple: until the international board change the rules, I can only play 11."