Madrid trailed 2-0 at the break after early goals from Hakim Ziyech and David Neres put the visitors in control of the tie, 3-2 up on aggregate with 45 minutes to play.
Vazquez, Vinicius injured in horror first half
Real Madrid was hit by a pair of first-half injuries in its Champions League last-16 second leg against Ajax at the Santiago Bernabeu.
The reigning European championwas forced into a pair of changes before the break, with Lucas Vazquez and Vinicius Junior hobbling out of the match in quick succession.
Gareth Bale replaced Vazquez - who could be seen nursing his thigh on the bench - and was again jeered by the Bernabeu crowd, having been whistled off in Saturday's Clasico defeat to Barcelona.
Marco Asensio came on for teenage winger Vinicius as Madrid - already without suspended captain Sergio Ramos - looked to rescue the tie.
