Gunners boss Arsene Wenger had called for a response following last week's shock Capital One Cup penalty shoot-out defeat at Bradford - and got it as the visitors surged into a 3-0 half-time lead following Lukas Podolski's well-taken goal and a brace from Cazorla.
The Spaniard completed his treble on the hour, and although the Royals rallied with goals from substitute Adam Le Fondre and Jimmy Kebe, Arsenal made sure there would be no late drama when Theo Walcott slotted in a fifth with 10 minutes left.
Arsenal were ahead on 14 minutes as Kieran Gibbs clipped the ball through to Podolski, who expertly took the bounce in his stride before smashing a left-foot shot past keeper Adam Federici.
It was 2-0 on 32 minutes. This time Podolski turned provider as the German charged down the left channel before chipping the ball back through the six-yard box where Cazorla arrived to head past Federici.
Before the Royals could mount any sort of fightback, Arsenal were 3-0 up.
Walcott's cross from the right was nodded back by Gibbs and Cazorla, with his back to goal, turned to hook the ball into the bottom corner.
The Royals defence was breached again on the hour as Cazorla grabbed his hat-trick, drilling the ball in at the far post after Jack Wilshere had released Podolski down the left.
The home fans at least had something to cheer on 66 minutes when Le Fondre pulled a goal back, and they closed the gap further when Kebe slotted home after beating the offside trap
Hopes of a remarkable comeback were, however, dashed with 10 minutes left when Walcott stepped inside before to slotting a curling effort into the far corner.