Ernesto Valverde's side had been due to host their bitter rivals on October 26, only for the game to be postponed amid concerns over civil and political unrest in Catalonia.
The sides are tied on 35 points apiece at the top of the LaLiga standings after 16 games, with Barcelona in first place thanks to a superior goal difference.
In the last Clasico, played at Camp Nou in March, Ivan Rakitic scored a delightful winner in a 1-0 victory to send Barca 10 points clear at the summit.
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Captains Lionel Messi and Sergio Ramos were also involved in a flashpoint during a fiery clash, but Barca's talisman was withdrawn at half-time against Villarreal with a groin problem.
Heading into Wednesday's clash, Messi and Karim Benzema are the league's joint top scorers with 12 goals each.
Kick-off for #ElClasico has been set for 2:00PM ET on beIN SPORTS and beIN SPORTS CONNECT, pre-game coverage begins at 1:00PM ET.