Dzsenifer Marozsan gave the French side the lead after just five minutes and within 20, the tie was all but over, with Ada Hegerberg scoring two quickfire goals before completing her hat-trick on the half-hour mark.
Barca, bidding to become the first ever Spanish side to win the competition, had boasted a proud record of having not conceded in 660 minutes of European action heading into the match.
However, that record was soon shattered, with Shanice van de Sanden beating her marker down the right and crossing to Marozsan, leaving the German with an easy finish.
The Dutchwoman proved to be a constant threat down the flank and less than 10 minutes later she had her second assist, setting up Hegerberg to tuck home to double the French side’s lead.
Minutes later, any faint hopes Barca still had were all but over. This time, the ball came from the left, with Amel Majri providing the assist and Hegerberg yet again on hand to put the ball in the back of the net.
Then came the Norwegian’s hat-trick. The Ballon d’Or winner fed Lucy Bronze down the right and was on hand to capitalise on Sandra Panos’ suspect goalkeeping to complete her treble.
After the break, Eugenie Le Sommer drove an effort wide and Hegerberg forced a further save from Panos, while Barca squandered a presentable chance through Lieke Martens. The Catalans pulled back a late consolation through Asisat Oshoala's 89th-minute effort but the day belonged to Lyon and Hegerberg.
In addition to their fourth straight European crown, Lyon have also won 13 consecutive Division 1 Feminine titles and have won their fifth treble.