Akinfeev was eager to prove his worth once more after doing so at the summer's World Cup, with a save off a shot from Nacho Fernandez on 37 minutes.
Alfa Semedo, however, scored a late winner for the 10-man visitors. Showed flashes in the second half, as he zipped across the attacking line and linked well with Alvaro Odriozola.
From there Madrid went side to side and back again.
Akinfeev was sent off in the 96th minute after referee Ovidiu Hategan dismissed the Russian goalkeeper for dissent after he pleaded with Hategan to punish Madrid centre-back Raphael Varane for what he felt was an attempt to win a late penalty.
"Madrid are a great club and they have enough players for two squads", he said.
A late rally on the field failed to yield a goal that would have secured a second straight win for United in Group H and it proved to be another frustrating night for Mourinho, who is under some pressure after United's underwhelming start to the season. How they could have done with a handy hat-trick here.
Real Madrid mounted wave upon wave of attacks, and wasted several chances in the first half.
"You cannot block out the sun with one finger, but that is the past, and we cannot rely on that now".
The Spanish side were rarely troubled in the goalless draw, with United's Marcus Rashford coming closest to scoring when his free-kick clipped the top of the bar.More news: Fortnite no estará disponible en Google Play Store
Despite the late drama, Real still couldn't find a way through and the seconds seeped away. "We need to create scoring chances, I'm sure that sooner or later we will start scoring". But this was not some schmaltzy rerun. He came on against Roma and scored.
And Lopetegui, rather than read too much into the performance, merely suggested the result was a freak one.
Bale was left behind in Madrid. All three are 22. This game marks three in a row without a win. Sergio Ramos got a rest.
DF Dani Carvajal, 5 - Off injured after 43 minutes. Marcelo, Isco and Gareth Bale all missed out through injuries of their own.
SI TV is also now available on fuboTV.
"It'll be a really tough game against a side of real pedigree". Without him there isn't the same threat. "He understood he had to be a leader and took that mantle".
Akinfeev denied Kroos a chance to make amends but Fedor Chalov should have made it 2-0 after more poor defending, instead hitting a tame shot Navas saved easily. And the space stays vacant. Madrid did hit the woodwork three times. They needed directness and something different.