Gerardo Martino's men were leading the Segunda Division B side 4-1 from the first leg and pulled further away through goals from Pedro (31), Cristian Tello (66) and Neymar (88).
Getafe, who routed Girona 4-1 to complete a 5-2 aggregate win, are next up for the Spanish champions.
Osasuna could meet Real Madrid in the last 16 after beating Malaga on away goals.
The Pamplona club had secured a 3-3 draw in the first leg at the Rosaleda and went ahead on home turf through Weligton's early own goal. Eliseu Pereira made it 1-1 on the hour mark but Malaga could not find the second goal they needed to progress.
Real Madrid on Wednesday welcome third-tier Olimpic Xativa to the Bernabeu. Away goals could be an area of concern for Carlo Ancelotti's men after the first leg ended goalless.
Jeremy Perbet's 57th-minute goal settled a 1-0 win at Elche and sent Villarreal through as 3-2 aggregate winners, while Levante overturned their 1-0 first-leg loss to brush Recreativo Huelva aside 4-0 in the return fixture.