The victory lifted Barcelona back to the top of the Spanish league with 21 points, while Madrid were left languishing in ninth place with 14 points.
Messi again showcased his multi skillset with a dazzling display of playmaking and finishing while leading Barcelona to another win.
Barcelona are unbeaten after starting with seven straight wins and drawing with Atletico Madrid last week.
Neymar is accused of evading 20.04 million US dollars in taxes from 2011 to 2013 by using front companies to hide the true value of his income.
The Argentine coach praised Barcelona's star Lionel Messi, who scored 27 goals in 34 matches between both sides in all competitions.
Pique criticized Spanish Prime Minister Mariano Rajoy for the way the government and police dealt with Sunday's plans for a referendum
Barcelona played behind closed doors amid the disputed referendum over Catalonia's independence on Sunday.
Wijnaldum said they would have been happy if he made the move to FC Barcelona as it could have helped his career.
The ugly slog of a match was interrupted in the 90th minute when a fan invaded the pitch to approach Messi, before being escorted off.
The Spanish giants don't seem to miss their winger as it has been Lionel Messi who has been netting in goals consistently since the Brazilian's departure.
Dembele was injured during Saturday's Spanish league match at Getafe, when he needed to be substituted in the 28th minute. Barcelona won the match 2-1.
There was a lot of speculation surrounding Coutinho as to where he would be playing this season as he missed the start of the season.
Barcelona won the match but lost Ousmane Dembele, its biggest offseason signing, midway through the first half because of an apparent muscle injury.
"I never thought about the possibility of being signed by Barcelona, because my idea was to triumph in Real Madrid," said Isco.
"If you leave Messi with an open field you know what's going to happen," said an upset Juventus coach.
Mbappe has been added to a glittering assembly of attacking talent that includes Brazil star Neymar, striker Edinson Cavani, and wingers Angel Di Maria and Julian Draxler.
With Paris Saint-Germain spending massively, French clubs paid out 697 million euros ($830 million) and made 619 million euros ($736 million).
Paulinho has been in superb form this year, having scored 12 goals in 29 matches for Evergrande across all competitions.
FC Barcelona had targetted the Brazilian player from the start of the summer transfer window but Liverpool kept rejecting the bids made despite Coutinho handing in his transfer request.
Now the pressure is on Dembele to prove his worth and show that Barcelona did the right thing by choosing him to play alongside Lionel Messi and Luis Suarez.
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