For nearly a decade the showdown has been defined by the battle of individual icons Cristiano Ronaldo and Lionel Messi, but neither player will feature on Sunday, with Ronaldo moving to Juventus and Messi sidelined with a fractured arm.
Nevertheless, the show must go on and their absence paves the way for new stars to ascend to greatness in the hallowed arena.
Victory for Barca will ensure they return to the top of the table, but struggling Madrid can reduce the gap between them to just one point with a win.
|Game||Barcelona vs Real Madrid|
|Date||Sunday, October 28|
|Time||3:15pm GMT / 11:15am ET|
|Stream (US only)||fubo TV (7-day free trial)|
TV Channel, Live Stream & How To Watch
In the United States (US), the game can be watched live and on-demand with fuboTV (7-day free trial).
New users can sign up for a free seven-day trial of the live sports streaming service, which can be accessed via iOS, Android, Chromecast, Amazon Fire TV, Roku and Apple TV as well as on a web browser.
|US TV channel||Online stream|
|beIN Sports||fubo TV (7-day free trial)|
In the United Kingdom (UK), the game can be watched live on TV on Eleven Sports 1 and it can be streamed online via the Eleven Sports app.
|UK TV channel||Online stream|
|Eleven Sports 1||Eleven Sports|
Squads & Team News
|Goalkeepers||Ter Stegen, Cillessen, Ezkieta|
|Defenders||Pique, Semedo, Lenglet, Alba, Chumi, Umtiti, Vermaelen|
|Midfielders||Rakitic, Busquets, Coutinho, Arthur, Rafinha, Roberto, Vidal, D. Suarez, Samper, Alena|
|Forwards||L. Suarez, Dembele, Malcom, Munir, Messi|
The chief absentee for Barcelona is Messi, who is recovering from a fractured arm. The Argentine was replaced in the starting XI by Rafinha for the Champions League game against Inter and he continues in that role on Sunday.
Barca are also contending with injuries to defensive duo Samuel Umtiti and Thomas Vermaelen, with Gerard Pique and Clement Lenglet paired in central defence.
Barcelona XI: Ter Stegen; Sergi Roberto, Pique, Lenglet, Alba; Rakitic, Busquets, Arthur; Rafinha, Suarez, Coutinho
|Position||Real Madrid squad|
|Goalkeepers||Navas, Casilla, Courtois|
|Defenders||Carvajal, Vallejo, Ramos, Nacho, Varane, Marcelo, Odriozoloa, Reguilon|
|Midfielders||Kroos, Modric, Casemiro, Valverde, Vazquez, Llorente, Asensio, Isco, Ceballos|
|Forwards||Diaz, Benzema, Bale, Vinicius Junior|
Marcelo starts despite suffering a knock in the Champions League against Viktoria Plzen. Concerns over the availability of Mariano Diaz and Dani Carvajal see Nacho Fernandez and Karim Benzema start.
Real Madrid XI: Courtois, Nacho, Marcelo, Ramos, Varane, Casemiro, Kroos, Modric, Isco, Bale, Benzema
Betting & Match Odds
Home side Barcelona are the favourites to win the first Clasico of the season with bet365 giving odds of 19/20. Real Madrid's chances of victory are rated 13/5 and a draw is available at 14/5.
With much of the focus ahead of the Clasico on the fact that both Ronaldo and Messi will be absent, it has allowed some attention to be drawn away from the fact that Real Madrid have been out of sorts.
Julen Lopetegui is facing serious questions over his future following a poor run of form, in which Los Blancos went five games without a win and dropped to eighth in La Liga. Tuesday's win against Viktoria Plzen brought some relief to the former Spain boss, but the result against Barca will be much more important.
Barca, on the other hand had raced to the summit of La Liga and, despite enduring an inconsistent patch towards the end of September, have laid down a marker both domestically and on the continent when it comes to the pursuit of titles this season.
The recent enforced absence of Messi did little to hamper Ernesto Valverde's men against both Sevilla and Inter, so it is clear that the squad are well equipped to cover, but there will no doubt be an added psychological edge to the game against their rivals.
It may be early in the season, but the outcome of Sunday's game could well have far-reaching consequences; for Barca it would help propel them on in their relentless assault for the title and for Real it could be decisive point in their campaign, not to mention Lopetegui's tenure.