Ajax secured a place in the Europa League despite suffering a 4-1 reversal in their Champions League Group D clash at Real Madrid.
Goals from Ronaldo, Jose Callejon (two) and Kaka capped a routine success for Jose Mourinho's side who had already booked their spot in the last 16 as runners-up.
Derk Boerrigter hit a consolation for the visitors who finish in third spot in the pool following Manchester City's failure to beat Borussia Dortmund in Germany.
Madrid welcomed the Dutch champions to the Bernabeu safe in the knowledge that the hard work was already done.
However, Mourinho stuck to his word by naming a strong line-up with Ronaldo and Karim Benzema involved from the start.
Frank De Boer's men had come into the contest buoyed by a 3-1 success over rivals PSV Eindhoven but never looked like upsetting a Madrid side that had won 13 of their previous 16 Champions League matches on home turf.
The hosts had the ball in the net early on but Benzema's close range finish from Kaka's centre was correctly ruled out for offside.
Fabio Coentrao then saw a shot cannon back off the post before the Bernabeu was finally on its feet in celebration when Ronaldo netted his 21st goal of the campaign.
Benzema broke the offside trap with a clever run down the right following an incisive pass from Luka Modric. The Frenchman cut in and drew Kenneth Vermeer before picking out Ronaldo who thundered the ball into the roof of an empty net.
It was a big blow for the visitors and they struggled to contend with a Real side that was still operating in second gear.
A succession of Ronaldo free-kicks ensued without the concession of a second but there was no surprise when Callejon eventually doubled the advantage just shy of the half hour mark.
The midfielder raced onto Modric's through pass and coolly slipped the ball in off the far post to leave Ajax with a mountain to climb.
The Dutch outfit had rarely threatened and had their only effort of the half three minutes before the interval when Viktor Fischer's deflected shot was easily claimed by Antonio Adan, standing in for Iker Casillas.
The same pattern continued after the break and it took just four minutes for Madrid to add a third.
Kaka was allowed a free run at goal and unleashed a 25 yarder that flew into the top corner.
The hosts sat back thinking the job was complete and to their credit, Ajax rallied.
Christian Eriksen set up Daley Blind to fizz just wide while the Danish midfielder brought the best out of Adan with a fierce shot.
The visitors looked like a different side and earned a lifeline on the hour mark when Boerrigter took advantage of an error by Adan to steer the ball into an empty net.
The forward then saw a smart curler well saved by the Madrid keeper as Ajax looked to pull off an improbable comeback.
But Real always had it in them to step up a level and substitute Alvaro Morata crossed from the right for Callejon to nod home a fourth two minutes from time.
It capped a bitter-sweet night for De Boer and his side who qualify for the Europa League despite being on the wrong-end of a drubbing in the Spanish capital.
MAN OF THE MATCH
Cristiano Ronaldo - Real Madrid: A modern great who broke the deadlock with an obligatory goal. At times he was unplayable without stepping out of his comfort zone.
REAL MADRID: Adan 6, Varane 7, Coentrao 5, Carvalho 6, Nacho 7, Khedira 6, Kaka 6, Modric 7, Callejon 7, Ronaldo 8, Benzema 7. Subs: Pepe 6, Rodriguez 6, Morata 5.
AJAX: Vermeer 6, Alderweireld 5, Moisander 6, Blind 7, Van Rhijn 6, Poulsen 5, Eriksen 6, De Jong 6, Boerrigter 7, Hoesen 6, Fischer 7. Subs: Schone 6, Sana 6, Enoh 6.