It has been a difficult week for Portuguese star Ronaldo, who missed the 4-0 loss to Liverpool to mourn the death of his newborn son. He returned for the crucial match against the Gunners at the Emirates Stadium on Saturday.
However, it was Mikel Arteta's team who took control of the battle for the Champions League places with a 3-1 win.
Ronaldo scored his 22nd goal of the season on his return, reviving United's hopes after Nuno Tavares and Bukayo Saka had put Arsenal 2-0 up.
However, Ronaldo must regret allowing compatriot Fernandes take a second-half penalty with the game finely poised at 2-1.
Fernandes, who was United's regular penalty taker, came forward but hit the outside of the post from a staggered run-up. Arsenal went on to score again through Granit Xhaka, sealing victory.
Arsenal 3-1 Manchester United ratings
Sixth-placed United are six points from the Champions League places and could miss out on European football for only the second time since 1990.
Interim boss Ralf Rangnick said United could have changed the course of the match if Fernandes had not missed his penalty.
"Yes we have to take that, if you're 2-1 down and get a penalty ... it would have helped a lot if that was the equaliser and probably also changed the whole game, but it didn't and it only hit the post," Rangnick said.
The manager said he spoke to Ronaldo about his decision to hand penalty duties to Fernandes.
"He said he just didn't feel he should take it, that's why he said it would be better if Bruno took it," Rangnick said.
Despite Ronaldo scoring his 100th Premier League goal, it was another forgettable outing for United as Diogo Dalot twice hit the woodwork and the team failed to make their period of superiority count.
United next host Chelsea on Thursday, with their thoughts possibly moving on to the next season when Erik Ten Hag takes over as the new manager.