Copa del Rey holders Barcelona will begin the defence of their title with a round-of-32 tie against Villanovense, while Real Madrid were paired with Cadiz in Friday's draw.
The draw for this round of the competition is seeded, with the seven teams representing Spain in the Champions League and Europa League guaranteed to face outfits from Segunda Division B leagues and Tercera Division.
Atletico Madrid - winners in 2013 - will face Reus, while last year's finalists Athletic Bilbao will take on Linense.
Elsewhere, Sevilla will play Logrones and Valencia come up against Barakaldo, while Villarreal take on Huesca.
The four all-La Liga ties drawn out of the hat were Real Betis against Sporting Gijon, Levante playing Espanyol, Las Palmas taking on Real Sociedad and Rayo Vallecano meeting Getafe.
Ties will be played over two legs on December 2 and December 16, with winners progressing to the last-16 stage, which is also seeded.