Trailing 2-1 from the first leg in Amsterdam, an Ajax team brimming with young talent destroyed a hapless Real 4-1 on the night thanks to first-half goals from Hakim Ziyech and David Neres and second-half finishes from the superb Dusan Tadic and Lasse Schone.
While Marco Asensio had pulled one back for Real at 3-0 down with 20 minutes left, they deservedly crashed out 5-3 on aggregate, ending any hopes of retaining a title which they have won for the past three seasons and have held for more than 1,000 days.
Real have in past seasons found solace in the Champions League when struggling domestically, but this time found no respite from their current woes as Ajax produced a pulsating display of attacking football.
While the Spanish hosts could have found themselves 1-0 up after five minutes when Raphael Varane headed against the bar from 6 yards, it was merely a false opening as to what would follow.
Ajax took the lead soon after when Hakim Ziyech sidefooted home on seven minutes to level the scores on aggregate at 2-2, after Sergio Reguilon was caught in possession near the half-way line and Dusan Tadic provided the assist.
The inspired Tadic turned provider again 10 minutes later, playing in David Neres, who finished coolly from inside the box to put his team 2-0 up on the night.
Tadic had rolled Casemiro in midfield during the build-up in a sublime piece of skill which was ironically so often seen by Real Madrid legend Zinedine Zidane.
Real headed into half-time with boos ringing in their ears, but it was to get worse 15 minutes into the second half when Tadic curled the ball into the top corner.
While a lengthy consultation with the VAR was needed to determine whether the ball had gone out of play in the build-up, the goal eventually stood and Ajax were 3-0 to the good and 4-2 up on aggregate.
Real eventually pulled one back through Marcus Asensio on 70 minutes, but Ajax’s Schone caught Thibaut Courtois out with a curled free-kick two minutes later to end any hopes of a late Real fightback.
The hosts also saw Nacho sent off for a second yellow card as their rule as kings of Europe came to an ignominious end.
Much of the focus will be on the meek submission of Santiago Solari’s men, who went into the game under immense pressure following lackluster displays in back-to-back defeats to arch rivals Barcelona.
But instead of bouncing back they proceeded to fold in the face of a relentless Ajax team that exuded the youthful energy Real are so badly lacking.
With captain Sergio Ramos suspended and watching from the stands, the Spanish side looked rocky at the back each time Ajax broke.
They also failed to muster much from midfield as Luka Modric was again below par while the much-maligned Gareth Bale, who came on as a first-half substitute, was also ineffective.
Their only bright spark again was 18-year-old Brazilian Vinicius, although he was forced off with injury before half-time.
While it is undoubtedly the end of an era for a Real team in desperate need of rebuilding, plaudits must be handed to a vibrant Ajax who had 30-year-old Tadic and 19-year-old defender Matthijs de Ligt as among their standout performers.
The latter of those two could well be heading to Barcelona alongside 21-year-old teammate Frenkie de Jong next season, meaning Real have far from seen the back of the Ajax youngsters.
It was a night that signaled a changing of the guard in Europe, and no matter how far Ajax progress after booking their quarter-final berth, one thing is for sure, Real Madrid have been dethroned as the kings of European football.
TOTTENHAM PASS DORTMUND TEST
Joining Ajax in the last eight are Tottenham, who secured a comfortable 4-0 aggregate win over Borussia Dortmund by winning 1-0 on the night in Germany.
Spurs weathered a predictable early storm at a raucous Westfalenstadion before captain Harry Kane produced a smart finish on 48 minutes to put them out of sight in the tie.