Madrid coach Zinedine Zidane fielded a strong side, while Zaragoza boss, Victor Fernandez, perhaps mindful of his side's aim to return to the Primera Liga, fielded a team packed with substitutes.
The result was never really in doubt from the sixth minute when Raphael Varane was able to tap home from close range following a corner.
Lucas Vazquez doubled Madrid's lead in the 32nd minute after his side pressured Zaragoza into an error deep in their own half and although Zaragoza improved with the introduction of regular starters Luis Suarez and Alex Blanco, further goals from Vinicius Jr and Karim Benzema sealed Real Madrid's win.
Wednesday also saw Real Sociedad reach the last eight as Alexander Isak continued his form with two goals in their 3-1 win at home to Osasuna.
Villarreal needed goals in the last 10 minutes from Fernando Nino and Santi Cazorla to beat second division Rayo Vallecano, while cup holder Valencia needed a penalty shoot-out to go through after 120 minutes against Cultural Leonesa (who last week beat Atletico Madrid) ended goalless.
Granada also struggled to beat lower-tier opposition and it was only after extra time that Carlos Fernandez scored the winning goal in their exciting 3-2 win away to Segunda B (third tier) Badajoz.
Wednesday saw Athletic Club Bilbao qualify for the last eight after beating second division Tenerife out in a penalty shoot-out after the game had ended 3-3 after extra time. Athletic played for 118 minutes with a player less after goalkeeper Iago Herrerin was sent off in the second minute.
FC Barcelona entertains Leganes, while Sevilla visits second division Mirandes on Thursday night and the draw for the quarter-finals will be made on Friday.
( With inputs from IANS )