Having recently celebrated 1000 days as the best team on the continent, Madrid saw their hopes of a fourth straight title ended in dramatic fashion.
The Blancos had a 2-1 first-leg advantage to defend but Ajax pulled off a shock win at the Bernabeu, triumphing 4-1 in the Spanish capital and heaped pressure on manager Santiago Solari.
The game saw Madrid's biggest ever margin of defeat in a home knockout game in European competition and was only the third time in history that they'd lost four home games in a row at the historic stadium.
bet365 made that score line a 50/1 (51.0) chance before kick-off on Tuesday, with some firms as big as 60/1 (61.0) about such an outcome. As a result, Ajax have made the quarter finals of the competition for the first time in 22 years.
Madrid had been in stumbling in the run up to the clash with Erik ten Hag's men, but few expected the holders to crash out of the Champions League at the last 16 stage, let alone in such emphatic fashion.
However, Madrid's dismal displays of late saw some punters take a chance on the Dutch side, who were backed into 9/2 (5.50) to turn the tie around at the Bernabeu and 18/5 (4.60) to win the second leg. The historic victory has seen Ajax cut to 25/1 (26.0) in the outright betting.
Tottenham secured their place in the last eight with a 1-0 win over Borussia Dortmund in the evening's other game, giving Mauricio Pochettino's side a 4-0 aggregate win over the Bundesliga team. Spurs are now a 14/1 (15.0) for European glory this term with bet365.
The same firm make Manchester United 20/1 (21.0) chances to overturn their 2-0 first leg defeat against Paris Saint-Germain on Wednesday. Ole Gunnar Solskjaer's side have been in flying form domestically and are back in the race for a top four spot in the Premier League but the bookies expect PSG to prove too strong for United at the Parc des Princes.
Odds correct at the time of publish. Please gamble responsibly.