The visitors took the lead after just 18 minutes when Patricia Guijarro struck with a deflected shot from the edge of the penalty area.
An own goal from Babett Peter saw Barca double their lead just after the half-time break before Lieke Martens volleyed the champions 3-0 ahead.
Captain Alexia Putellas wrapped up the victory with Barca’s fourth goal to hand her team a winning start to the new season.
The game was Real Madrid’s first match since they were official formed. Los Blancos hadn’t really bothered with women’s football until they took over CD Tacon.
Barca had played Tacon previously, winning 9-1 and 6-0 last season, but this was the first time the two teams have met since the Real Madrid team were officially formed.