Robert Lewandowski plundered his 13th and 14th goals of the season as Barcelona ended Real Madrid’s 42-game unbeaten LaLiga run with a 4-0 drubbing at the Bernabeu Stadium.
The Poland international opened the scoring with a 54th-minute strike and headed home a second two minutes later before Lamine Yamal and Raphinha struck to complete the scoring.
It proved a barren night for Madrid superstar Kylian Mbappe, who was repeatedly caught offside in his first El Clasico and saw a first-half strike ruled out by VAR as the champions failed to make the most of early pressure.
Ayoze came off the bench to lift Villarreal into third place with a 2-1 victory at Real Valladolid after Mamadou Sylla's penalty had cancelled out Thierno Barry's opener.
Alaves keeper Antonio Sivera's own goal handed Rayo Vallecano a 1-0 home win despite playing for 68 minutes with 10 men following defender Abdul Mumin's first-half dismissal.
The unfortunate Sivera saw Gerard Gumbau's shot come back off the woodwork and hit him on the back before ricocheting into the net.
Alex Munoz fired Las Palmas to back-to-back league wins when his 42nd-minute goal secured a 1-0 victory over Girona.
Second-half goals from Willi Orban, Lutsharel Geertruida and Lois Openda sent RB Leipzig to the top of the Bundesliga table courtesy of a 3-1 home win over Freiburg.
Ritsu Doan had put the visitors ahead in the battle of the sides lying in second and third places respectively at the start of the day, but Leipzig's response was concerted.
Romano Schmid's last-minute equaliser dented Bayer Leverkusen's title defence as Werder Bremen fought back twice to draw 2-2.
Victor Boniface, who returned to the Leverkusen team after suffering minor injuries in a car crash last weekend, opened the scoring and Felix Agu's own goal restored the visitors' advantage with Marvin Ducksch having levelled only for Schmid to intervene at the death.
Alexis Claude-Maurice's double secured a 2-1 comeback win for Augsburg at home to Borussia Dortmund.
The visitors, who had substitute Almugera Kabar sent off for a second bookable offence in stoppage time, took a fourth-minute lead through Donyell Malen, but Claude-Maurice levelled before the break and then snatched victory five minutes into the second half.
Deniz Undav and El Bilal Toure struck as Stuttgart beat lowly Holstein Kiel 2-1 with Armin Gigovic replying for the visitors on a day when both sides finished down to 10 men with Jeff Chabot and Fiete Arp receiving their marching orders.
Meanwhile, St Pauli's home clash with Wolfsburg ended goalless.
In Serie A, Napoli skipper Giovanni Di Lorenzo scored the only goal as the leaders beat Lecce 1-0 at the Diego Armando Maradona Stadium.
Ademola Lookman and Mateo Retegui scored twice each in Atalanta's 6-1 demolition of Verona with Marten de Roon and Charles De Ketelaere supplying their remaining goals and Amin Sarr responding for the visitors.
Jonathan David and Mohamed Bayo both struck in stoppage time as Lille left it late to snatch a 2-0 Ligue 1 victory at Lens.
Himad Abdelli, Jean-Eudes Aholou, Ibrahima Niane and substitute Bamba Dieng were on target as Angers beat St Etienne 4-2 despite Zuriko Davitashvili twice levelling.
Mama Balde's first-half goal proved decisive as Brest won 2-1 at Reims, where Romain Faivre had opened the converting a penalty with Joseph Okumu scoring for the hosts.
