Cristiano Ronaldo's early goal in Turkey means that the Spanish champions are 4-0 ahead in the tie and are just 45 minutes away from booking their place in the semi-finals.
Jose Mourinho's side started the game the brighter of the two teams and created the first chance as early as the third minute.
Four minutes later Ronaldo put Madrid ahead when he smashed home from close range after latching onto Sami Khedira's pass.
The Portuguese forward came close to making it 2-0 moments later but was denied by a good Muslera save.
Madrid continued to dominate proceedings at the Turk Telekom Arena and had another good chance on 23 minutes, this time Muslera making a one-handed save from Di Maria's shot.