The Gunners, aiming to become champions for the first time since 2003-04, went ahead at Emirates Stadium through Gabriel Martinelli’s left-footed strike.
It was his sixth goal in six league matches.
Bukayo Saka doubled the lead in the 43rd minute, finoshing off abcurling pass from Brn White.
Granit Xhaka made it 3-0 with a first-time finish from Leandro Trossard’s assist, before Jeffrey Schlupp pulled one back from close range following a corner for Palace’s first goal in five matches.