After opening with a laboured 1-0 win over Dinamo Zagreb on matchday one, Jose Mourinho's men looked more in the mood on Tuesday night and eased to the three points thanks to goals by Cristiano Ronaldo, Kaka and Karim Benzema.
The result was perhaps a touch harsh on an Ajax side who matched their hosts for large swathes of the first half, but Madrid's clinical finishing proved the difference.
The Dutch side started brightly and had a shot on target inside the first minute, Christian Eriksen taking aim from just outside the area to force a good parry from Iker Casillas.
Eriksen took another punt from distance on seven minutes but this time fired high into the Bernabeu stands, while two minutes later Benzema did likewise for the hosts at the other end.
Casillas was again called on to preserve his clean sheet on 15 minutes when Siem De Jong struck a volleyed effort from inside the area, the Madrid goalkeeper reacting well to make an instinctive stop.
Madrid were struggling to put their stamp on the game but nearly went ahead against the run of play three minutes later, Mesut Ozil pulling the ball back for Benzema to fire a low shot wide of the far post.
The chance appeared to galvanise the hosts, and moments later Ajax goalkeeper Kenneth Vermeer saved at the feet of Ronaldo after the Portuguese had been played clean through.
With 25 minutes on the clock the hosts went ahead, and it was no more than just reward for an improved spell of possession.
Kaka and Ozil combined well in the build-up, and after the ball was swept out to Benzema, the Frenchman delivered a perfect cross for Ronaldo to tuck home.
Despite settling well after going behind, Ajax conceded again four minutes before the break.
Xabi Alonso fired a long ball down field for Ronaldo to tee up Kaka, and the Brazilian showed all of his class as he fired home low into the right corner.
Ajax would have felt aggrieved to be down at the break after matching Mourinho's troops in the opening 45 minutes, and their mood darkened further on 49 minutes when Benzema made it three.
Another Alonso punt downfield did the damage, Alvaro Arbeloa collecting the ball and finding Kaka, who in turn set up Benzema for a cool finish beyond the helpless Vermeer.
De Jong and Eriksen had further chances for Ajax as the visitors strove to find a way back into the match, but the Madrid goal held firm.
The closest Ajax came to getting on the scoresheet came eight minutes from time when Eriksen's free-kick found the head of Jan Vertonghen but Casillas was equal to the task, making a brilliant stop to turn the ball round for a corner.
The win sees Madrid maintain their two-point gap to Lyon at the summit of the group, while Ajax are third on one point and will be desperate for their first win of the group phase when they face Dinamo in Zagreb on matchday three.