Depor's two Barcelona-born players scored in each half to secure victory at the Nou Camp for the second season in a row.
Earlier in the evening well taken goals in each half from Brazilian duo Ronaldo and Roberto Carlos earned Real Madrid a comfortable win over goalshy Celta at a rain-soaked Balaidos.
Saturday's results mean Deportivo lead the table with 18 points from seven matches, two ahead of Real and Valencia, who led the standings before the weekend's matches and can reclaim top spot if they win at home to bottom club Espanyol on Sunday.
Barca started strongly against Depor but, despite some sparkling individual play from Ronaldinho, they were unable to find a way past their opponents' well-drilled defence.
It was former Barcelona ball-boy Luque who opened the way to Depor's victory when he got his foot to a fine curling pass from defender Joan Capdevila four minutes before the break.
Sergio made sure of the win when he drilled in from the edge of the area after playmaker Juan Carlos Valeron had carved open the Barca defence and cut back a perfect pass into his path.
A second successive defeat means that Barca, who have yet to win a league match at their own stadium this season are now nine points adrift of the leaders.
CAGEY START
The game at Vigo began in cagey fashion as the teams sized each other up in midfield in the first 10 minutes, but with Zinedine Zidane at the helm it did not take long for Real to get into their stride.
The Frenchman combined well with Ronaldo before firing a shot across the face of the goal following a David Beckham free kick on 11 minutes and Raul was denied an opener when Cavallero blocked a sharp effort soon after.
Ronaldo then went close with an attempted backheel in teh 20th minute after a low cross from Luis Figo, but only four minutes later he opened the scoring when he provided the finishing touch to a sharply executed counter-attack.
Zidane began the move just inside Celta's half as he sprayed the ball wide to Figo, who cut a first time pass to Ronaldo's feet. The Brazilian took one more step before cracking a precise right-foot shot past Cavallero for his sixth goal of the season.
Real eased up after scoring but went within a whisker of extending their lead as Helguera hit the bar when he got his head to a goal-bound Beckham free kick.
Celta looked desperately short of ideas in attack as they failed to manufacture a single scoring chance in the first half and it was only when substitute striker Catanha came on after the break that they managed to create any danger.
But just as they appeared to be working their way back into the game Real hit them again on 65 minutes.
Zidane swung the ball out to Roberto Carlos on the left and the Brazilian defender controlled it with his chest and checked past Velasco before firing home from close range.
