Going into the tournament, the winners were assured a place for the 2016–17 UEFA Europa League Group stage.
However, since the two finalists, Barcelona and Sevilla, both qualified for the 2016–17 UEFA Champions League, respectively by winning the 2015–16 La Liga title and the 2015–16 Europa League, the cup winner's place in the 2016–17 Europa League group stage instead passed to the fifth-place team in La Liga, Athletic Bilbao.
Barcelona entered as the defending champions after winning the 2014–15 edition.
The draw for the Round of 32 was held on October 16, 2015, in La Ciudad del Fútbol.
This rule was also applied in the Round of 16, but not for the Quarter-finals and Semi-finals, in which the order of legs was based on the luck of the draw.