The result moves them to within four points of leaders Rennes, and provides them with a much-needed boost ahead of their tricky-looking trip to the Spanish capital.
Lisandro stole the show, opening the scoring early on before wrapping up his hat-trick after the break, with other strikes coming from Miralem Pjanic and Michel Baston.
Lyon were straight at their opponents and Yoann Gourcuff rattled the bar with a thumping 25-yard free-kick with just seven minutes gone.
That set the tone for what was to follow, with Lisandro making it 1-0 five minutes later.Jimmy Briand broke through and pulled back for the waiting striker who composed himself and finished.
Four minutes later it was 2-0. Briand and Lisandro combined again, this time for the benefit of Pjanic who ran on to Lisandro's cross to score.
Arles were barely in the game but did have a 26th-minute chance, Camel Meriem crashing against the post.
Gourcuff's volley that was easily saved by Vincent Plante was the last action of the first half, but the first action of the second saw Lyon make it three.
A pinpoint cross from Delgado picked out Lisandro and he strolled on the the ball and headed home.
Three minutes later, in the 54th, he made it 3-0. A gap in the Arles defence allowed Bafetimbi Gomis to power through on goal but, with Lisandro in support, he squared for his team-mate to complete his treble.
