After winning Europe's elite club tournament in three consecutive years under Zinedine Zidane, a tough first campaign since the French icon's departure was capped in remarkable fashion on Tuesday in a 5-3 aggregate loss.
Madrid fell apart in the first half and saw their 2-1 first-leg lead overturned in the opening 20 minutes by goals from Hakim Ziyech and David Neres as Ajax ran riot.
The irrepressible Dusan Tadic added another with a controversial second-half strike, leaving Madrid requiring three goals to stay in the competition, and although Marco Asensio got one back, a fourth home defeat in a row never looked in doubt as Lasse Schone made it four.
With two of those reverses coming at the hands of bitter rivals Barcelona last week before this humbling, pressure will undoubtedly build on head coach Santiago Solari's position.
The unmarked Raphael Varane headed against the crossbar inside five minutes, but Ajax settled into the contest thereafter and two superb pieces of creative play from Tadic swiftly wiped out Madrid's away goals.
Tadic first darted in behind Nacho Fernandez to square for Ziyech to sidefoot into the bottom left corner and then the Serbia international left Casemiro in a spin and played in Neres for a calm finish.
Ajax passed up further chances before a horrible half for the hosts was compounded by injuries to Lucas Vazquez and Vinicius Junior in quick succession.
Substitute Gareth Bale, jeered off the pitch against Barca, was again whistled by his own supporters and almost gifted Ziyech a third goal before striking the post at the other end.
Madrid scarcely improved after the restart and Tadic was rightly the man to put the tie beyond them, slamming into the top-left corner before a lengthy delay as VAR finally advised the referee that the ball had not gone out of play earlier in the move.
A belated response saw Asensio slide a finish beyond Andre Onana, but there was no let up in Ajax's attacking ambition and a glorious Schone free-kick caught out the scrambling Thibaut Courtois, before a frustrated Nacho was sent off in stoppage time.
What does it mean? Season ended in a week
In the space of seven days, Madrid played three home games, lost three home games and exited two competitions, also slipping 12 points behind in LaLiga. That two of the defeats were to Barcelona and the other saw their incredible European run ended makes matters more painful still. Solari's hopes of remaining in this job beyond the end of the season are surely over.
Tadic tortures Madrid
There were stars everywhere in this Ajax team, with Frenkie de Jong controlling the midfield and Neres tying Dani Carvajal in knots. But Tadic was undoubtedly the star of the show. He looked a threat every time he got on the ball and the piece of skill that sold Casemiro and led to the second goal was simply breathtaking - as was his finish for the third.
Suffering without Sergio
If it was difficult to pinpoint the outstanding performer in the visiting ranks, it was tougher still to find Madrid's chief culprit. It might be that the man who did the most damage to their cause was not even involved on Tuesday. Regardless of protestations that a first-leg yellow card was unintentional, Sergio Ramos' suspension left Madrid with a hapless back line.
Key Opta facts
- Real Madrid are the first reigning Champions League winners to fail to qualify for the quarter-final stage since Chelsea in 2012-13 (knocked out in the group stage).
- Madrid's 4-1 defeat to Ajax was their biggest ever margin of defeat in a home knockout game in European competition.
- Ajax progressed through a Champions League knockout stage tie for the first time in 22 years, last doing so in the 1996-97 campaign when the Dutch side prevailed against Atletico Madrid in the quarter-finals.
- Madrid have lost four successive games at the Bernabeu for just the third occasion in their history – also doing so in 1995 and 2004.
Madrid will be relieved to get away from the Bernabeu when they go to Real Valladolid on Sunday. Ajax host Fortuna Sittard next but could be forgiven for having more than one eye on the Champions League quarter-final draw.