Portugal international Goncalo Guedes fired Valencia into the lead in the 35th minute with a thumping shot from inside the area which was too powerful for Madrid goalkeeper Keylor Navas.
Real Madrid coach Carlo Ancelotti fended off questions about his future after the Champions League holders were dumped out in the semi-finals by Juventus 3-2 on aggregate on Wednesday.
Thomas Partey scored his first goal for Atletico Madrid as they reached the last 16 of the King's Cup with a 1-0 home victory over third-tier Reus on Thursday that secured a 3-1 aggregate success.
Now, Real Madrid have never won the Spanish treble and are fighting tooth and nail in La Liga to prevent arch-rivals Barcelona scooping Champions League and domestic league and Cup titles for a second time.
Barca made a slow start to the campaign under their new coach but after beating Paris Saint Germain in the quarter-finals they are on course to repeat the treble success.
Barcelona have been haunted by their recent failures in the Champions League and there are concerning signs for the Catalans as they prepare for Tuesday's last-16 first leg away to Olympique Lyonnais.
Atletico Madrid's Jackson Martinez scored his first goal for the club when he came off the bench and curled in a superb effort to seal a hard-fought 3-0 victory at Sevilla in La Liga on Sunday.
The Bavarians have now won the German league title a record 29 times.
Arsenal led a list of nine clubs who grabbed a second win in as many games in the Europa League group phase as France striker Olivier Giroud scored his 100th goal for the club in a 4-2 win at BATE Borisov on Thursday.
News of all that transpired on and off the football field.
The clinical Argentine Messi now has 11 goals in his last five games in all competitions and with record signing Ousmane Dembele injured and Luis Suarez rested, he put on a sensational show at Camp Nou to extend Barcelona's La Liga lead.
Lionel Messi, Luis Suarez and Neymar were all on target as holders Barcelona beat Athletic Bilbao 3-1 on Wednesday to overturn a deficit from the first leg and advance to the quarter-finals of the King's Cup.
The injury list in the La Liga keeps growing as the season progresses and this time Lionel Messi and Gareth Bale are the unfortunate victims...
FC Barcelona's midfield magician and the architect of tiki-taka football gets emotional farewell
Liverpool striker Daniel Sturridge was substituted with a thigh injury as the English Premier League club beat Bayern Munich 3-0 in a pre-season match in Germany on Tuesday.
Barcelona made a brisk start to the season with new coach Luis Enrique at the helm in place of Gerardo Martino and a host of additions to the squad, including midfielder Ivan Rakitic and goalkeeper Claudio Bravo.
Barcelona extended their near-perfect start to the season when Alexis Sanchez tapped in at the far post from Neymar's clever assist to secure a 1-0 win at home to city rivals Espanyol in La Liga on Friday.
Real Madrid maintained their pursuit for the title by defeating Malaga 3-1 late on Saturday.
Mesut Ozil quit Real Madrid to join Arsenal because he realised he no longer had the confidence of Real coach Carlo Ancelotti, the Germany playmaker said.
News of all that's transpired on and off the football field
Holders Real Madrid survived a huge scare when they lost 4-3 to Schalke 04 in the Champions League on Tuesday but squeezed into the quarter-finals 5-4 on aggregate thanks to record European marksman Cristiano Ronaldo.
Luis Suarez had the Barcelona fans chanting his name after he set up Lionel Messi to score the opening goal in their King's Cup semis.
News of all that's transpired on and off the football field
Champions Barcelona came through a gruelling La Liga test at a rainswept San Mames on Sunday, beating Athletic Bilbao 1-0 thanks to Ivan Rakitic's first-half header.
A late goal by Toni Kroos sealed victory as Real Madrid defeated an impressive Celta Vigo side 2-1 to win their first home La Liga game of the campaign on Saturday.
Cristiano Ronaldo scored his 400th goal for Real Madrid as Zinedine Zidane's side closed in on a first La Liga title since 2012, easing to a 4-1 win over Sevilla on Sunday while Neymar hit a hat-trick for Barcelona, who thrashed Las Palmas 4-1.
Barcelona seized control of their King's Cup quarter-final tie against Atletico Madrid when Lionel Messi followed up his saved penalty to score and secure a 1-0 first-leg victory at the Nou Camp on Wednesday.
To finish with dignity is how Robin van Persie wants to end his playing days on Sunday when he hangs up his boots after an 18-year career.
Ruthless Bayern Munich scored five goals in the first 35 minutes on the way to a 7-1 demolition of AS Roma on Tuesday which bore an uncanny resemblance to Germany's win over Brazil by the same score in the World Cup semi-final.
IMAGES from the soccer matches played in Spain and Italy on Saturday
Real Madrid set up a King's Cup semi-final against holders Atletico Madrid or Athletic Bilbao when they beat Espanyol 1-0 in their quarter-final, second leg on Tuesday for a 2-0 aggregate success.
The Champions League quarter-final between Liverpool and Manchester City is one of the most anticipated games of the season pitting the Premier League's runaway leaders against the top scorers in Europe's elite competition.
Alexis Sanchez hit a hat-trick as Barcelona swept aside Elche 4-0 to return to the top of La Liga on goal difference ahead of Atletico Madrid on Sunday.
Underlying tensions mean Luis Enrique will not be remembered with the same reverence as Pep Guardiola, even though he has delivered a similar trophy haul.
Real Madrid goalkeeper Keylor Navas says the signing of Belgium keeper Thibaut Courtois has not affected his desire to remain at the triple European champions as he emphatically ruled out leaving the club in order to be assured of first team football.
Barcelona's 2-1 loss at Ajax Amsterdam in the Champions League last week was down to a lack of intensity while Sunday's 1-0 reverse at Athletic Bilbao in La Liga exposed their relative physical frailty.
Barcelona's Lionel Messi, Luis Suarez and Neymar motored past 100 goals for the season.
The draw interrupted a run of four straight league wins for Zinedine Zidane's side and left them second on 67 points after 31 games, three behind leaders Atletico who thrashed Eibar 5-0 earlier in the day.
Messi stretched Barca's lead by finishing off a brilliant move with Luis Suarez in the 50th minute and the Uruguayan joined his close friend and strike partner on 15 league goals by robbing an Eibar defender and finishing inside the near post in the 68th.
France striker Karim Benzema hit out at those who questioned his work ethic as he tried to play down Real Madrid coach Carlo Ancelloti's suggestion that he shies away from hard work.
