Luis Suarez's hat-trick inflicted 'La Manita' on Real Madrid, whose 5-1 defeat to Barcelona in Sunday's Clasico left Julen Lopetegui on the brink.
A miserable afternoon saw Madrid also possibly lose Raphael Varane and Marcelo to injury, although Suarez was arguably lucky to stay on the pitch for his third goal after a studs-up challenge on Nacho Rodriguez.
Barca remained without Lionel Messi, Samuel Umtiti and Thomas Vermaelen, so they were unchanged for the Clasico against a Blancos side who stuck with a 4-4-2, with Nacho moving to right-back
However, Vinicius Junior was nowhere to be seen in the matchday squad, despite the teenage striker choosing to travel with the first team over turning out for Castilla after his one-match ban was lifted.
Madrid had gone five Clasicos without a win, their last victory coming in April 2016, but the Catalans haven’t beaten their arch-rivals on home soil for three years.
This was referee Jose Maria Sanchez Martinez’s second Clasico after he oversaw the Blaugrana’s 3-0 win at the Santiago Bernabeu last December.
That would be a sign of things to come as a long ball down the left was taken down by Jordi Alba, who got to the byline and cut back for Coutinho to tap in from close range.
Sergio Ramos’ clearance then fell straight to Arthur, whose curler from the D was parried away by Courtois at full-stretch.
However, Varane kneed Suarez in Madrid’s six-yard box and a VAR review gave Barca a penalty, which Suarez slotted into Courtois’ bottom left.
Lopetegui replaced the France defender with Lucas Vazquez for the second half, which signalled a change to a 3-5-2 formation.
It quickly paid dividends as Marcelo pounced on a cutback into the Catalans’ box, took it on his chest and poked it past Marc-Andre ter Stegen for his third goal in as many games.
A turning point came when Modric fired a shot hard and low on to the base of Ter Stegen’s right-hand post, while Ramos sent a diving header over the bar.
Ernesto Valverde responded by swapping Rafinha for Nelson Semedo so Sergi Roberto could push on, and the youth product promptly chipped a cross for Suarez to guide past Courtois with his head from some way out.
The Uruguayan was hugely fortunate to only see yellow after he tread on Nacho’s ankle in a 50-50, and more luck went the hosts’ way when Marcelo followed Varane off the field with an injury.
Sergi Roberto pickpocketed Ramos and laid off Suarez, who charged towards Courtois and delicately lifted the ball over the Belgian for what was surely game, set and Clasico.
Ousmane Dembele also helped himself to an assist during his cameo as fellow substitute Vidal headed the winger’s delivery across Courtois.
Suarez then forced the Belgian into a save, courtesy of a flicked finish from another Sergi Roberto cross, before an unmarked Karim Benzema planted a finish the wrong side of Ter Stegen’s far post in the Blaugrana’s box.
The result sends Barca top of La Liga, two points clear of Atletico Madrid, while Los Merengues languish all the way down in ninth place.
Barcelona 5-1 Real Madrid
Coutinho 11, Suarez pen 30, Suarez 75, 83, Vidal 87 (B) Marcelo 50 (RM)
Barcelona: Ter Stegen; Sergi Roberto, Pique, Lenglet, Alba; Rakitic, Busquets, Arthur (Arturo Vidal 84), Rafinha (Semedo 69), Suarez, Coutinho (Dembele 84)
Real Madrid: Courtois; Nacho, Varane (Vazquez 46), Ramos, Marcelo (Mariano 82); Modric, Casemiro, Kroos; Isco; Bale (Asensio 77), Benzema
Referee: Sanchez Martinez