The center back has not played since the November 5 trip to Chelsea in the Premier League after being injured while on worldwide duty with the Ivory Coast.
"He goes to surgery, the decision is made", the Portuguese said.
Sources told ESPN FC in September that Mourinho was unhappy with Mkhitaryan's contribution against United's top-six rivals, but the player appeared to have overcome his manager's reservations by making an impressive start to the season with two goals and five assists in all competitions.
United head in to the weekend action sitting 11 points adrift of Man City so they'll be hoping the leaders drop points at home to Tottenham on Saturday night which would give Mourinho's men the opportunity to close the gap on Sunday.
There has been some talk in Italy that Mkhitaryan and Mata are players Mourinho would consider offering in a swap deal to bring Inter's Joao Mario to Old Trafford, and while that exact deal may not come off there is a clear need for the United boss to address the No.10 situation as it stands. I had that experience before.
"I don't speak about players, especially players that belong to other clubs - there is no sense", he said.
"When you're cooking for 200-odd people, that's a lot of time, effort and money going straight into the bin".
"It was hard but it was good for my development as a manager too which is something that I always try to do".
A year ago United sold Morgan Schneiderlin to Everton and Memphis Depay to Lyon for a combined £37 million after both fell out of favour during Mourinho's first season at Old Trafford.
"I've nothing to say in relation to that", said Mourinho.
"I'm not a big defender of the January market", Mourinho told a news conference on Friday. That's why I was just being patient, waiting for my time. "But if you can buy one you would buy in June, with the chance a few months before, then great".