
Real's biggest win in Mestalla for more than 40 years leaves them with 25 points from 10 games, four points ahead of Villarreal, who beat bottom team Levante 3-0.
Veteran strikers Raul Gonzalez and Ruud Van Nistelrooy, helped by livewire winger Robinho, tore the injury-hit Valencia defence to shreds in a superlative first-half display.
The match was over by half-time, with Real 4-0 up. Many Valencia fans went home early - to dream of Ronald Koeman rebuilding their tattered team.
Earlier on Wednesday, Koeman had agreed to leave PSV Eindhoven and sign a two-and-a-half year contract with Valencia, where he will clearly have to work hard to restore morale.
On Monday, Valencia sacked Quique Sanchez Flores and put nursery team coach Oscar Fernandez on the bench against Real.
It was a night in the limelight that Fernandez will want to forget quickly.
His troubled team went behind after just 44 seconds, when Robinho carved open the home defence and set up Raul to score with his trusty left foot.
In the 25th minute Raul set up partner-in-crime Van Nistelrooy to make it 2-0. Valencia were shell-shocked, and it came as little surprise when, just five minutes later, the majestic Guti set up defender Sergio Ramos to add a third.
In the 37th minute Robinho again picked his way through, and this time he set up Van Nistelrooy to make it 4-0.
Miguel Angel Angulo scored a consolation goal for Valencia in the 59th minute - only for Robinho to make it 5-1 six minutes later.
"We were really in top form in the first half," said Raul. "That was our plan, to hit them with everything at the start."
Valencia captain David Albelda moaned that "we started the game badly ... and never really improved at all."
Valencia crash down to fifth with 18 points.
Barcelona - currently with 20 points from nine games - will retake second place from Villarreal if they win away to lowly Valladolid on Thursday.
Thursday's other game is between sixth-placed Espanyol and midtable Murcia.
Right now Barca are level on 20 with Atletico Madrid, who kept up their good form by beating Sevilla 4-3 in Wednesday's late game.
Atleti won the seven-goal thriller with goals from Maniche, Sergio Aguero and Maxi Rodriguez.
Luis Fabiano scored twice for Sevilla, their other goal was scored by Atleti defender Ze Castro in his own goal.
Earlier on Wednesday, Zaragoza had moved up to seventh with a 1-0 win away to Almeria, courtesy of a penalty put away just 12 minutes from time by Diego Milito.
In Wednesday's other early matches, Getafe beat fellow relegation prospects Athletic Bilbao, while Osasuna romped to a 3-0 win away to troubled Betis - increasing the pressure on Betis coach Hector Cuper.
Mallorca battled out a 1-1 draw away to Deportivo Coruna, and Racing Santander escaped from Huelva with a point after a goalless stalemate.
Levante are rock bottom with just one point. Valladolid have six, Getafe and Betis eight. Then come Deportivo and Huelva on nine, with Bilbao on 10.
DPA