Cakır had a reputation as one of Europe's brightest young referees heading into the game at Old Trafford but his dismissal of Nani for a high boot into the chest of Alvaro Arbeloa raised serious questions - while undoubtedly changing the course of the game.
Before the match at Old Trafford, Sir Alex Ferguson had said: "You hope in a game of this nature that you are going to get the best refereeing performance, on the same level as the players on the pitch.
"Mistakes will be made by players and the referee but you hope it will be a top performance. You hope to get nothing less than the best. An occasion like this deserves that."
Cakır, who is generally regarded as one of three best referees in Europe, is in UEFA's 'elite referee' category and is hoping to go to the 2014 World Cup in Brazil.
The 36-year-old Turk, with his authoritarian manner in the middle, is also highly thought of by the Turkish Federation and is regularly asked to take charge of the biggest games in the Super Lig, including the combustible derbies involving Besiktas, Fenerbahce and Galatasaray.
But Eurosport Turkey's Efe Yilmaz says: "Most fans don't like him. They think he behaves differently in Super Lig games and European games. Because of this reason they don't like him."
Cakır, who works in insurance in Istanbul, made his European debut in the UEFA Cup in 2008-09, a match between Twente and Schalke, before progressing to the Champions League in 2010 in a clash between Rubin Kazan and Barcelona.
In 2011, Cakır took his no-nonsense brand of refereeing to a Europa League game between Manchester City and Dynamo Kiev, dishing out eight yellow cards and claiming his first scalp from an English club, Mario Balotelli.
He continued to make a name for himself and was rewarded with the Champions League semi-final between Barcelona and Chelsea in 2012, when he punished John Terry's sly kick with a red card.
He became the youngest referee at the age of 35 to officiate at a European Championship, taking charge of several Euro 2012 games including the semi-final between Portugal and Spain when he showed nine yellows.
His card-happy reputation continued to grow when Steven Gerrard, playing for England against Ukraine in a World Cup qualifier in September last year, and then Chelsea's Gary Cahill at the Club World Cup, fell victim to him.
Cakir was even at the centre of controversy in the days leading up to the United-Madrid clash after he failed to give a penalty in a domestic game between Akhisar and Elazıgspor. Fans protested and the match was stopped for several minutes.
Tuesday's match against Real was not the first time Cakir had taken charge of a United game. He oversaw a Champions League tie with Benfica and last season's Europa League match against Athletic Bilbao. United have never won with Cakir in the middle.