In the Eagles' first game since the sacking of Gunners legend Patrick Vieira, Paddy McCarthy's crop were torn to shreds by the league leaders, as Saka struck a brace alongside efforts from Gabriel Martinelli and Granit Xhaka.
Jeffrey Schlupp pulled one back for the visitors midway through the second half, but a shock result was never on the cards at the Emirates, as Mikel Arteta's side recovered from their disappointing Europa League elimination in splendid fashion.
Despite being forced into a change before the first whistle blew - Joachim Andersen sustaining an injury in the warm-up and being replaced by James Tomkins - Palace dug deep defensively in the first half and unsurprisingly asked a few questions on the break.
Wilfried Zaha struck the post with 11 minutes gone, and Odsonne Edouard forced a smart save down low from Aaron Ramsdale five minutes later, although the offside flag soon went up.
However, Arsenal soon found their groove, and in the 29th minute, Martinelli's 13th Premier League goal of the season sent them ahead courtesy of a landmark assist from Saka.
Finding space between two Palace shirts, Saka received the ball from Ben White and crossed for Martinelli, who was forced onto his left foot by Joel Ward but arrowed a sublime effort into the far corner.
The Brazilian had immediately consigned his costly penalty miss against Sporting Lisbon in the Europa League to history, as Saka became the first player to reach double figures for goals and assists in the current Premier League season.
Not long after, Saka would go from provider to goalscorer thanks to more stellar work on the right from White, who fed his compatriot to curl home into the bottom corner in the 43rd minute.
Following the shortest of VAR checks for offside, Saka's strike stood as Arsenal entered the break with a richly-deserved two-goal cushion, and the tie was seemingly put to bed 10 minutes into the second half.
Fresh from making Premier League history with his treble of first-half assists against Fulham, Leandro Trossard was the architect of Arsenal's third, slipping in Xhaka to net an untidy finish through the legs of Joe Whitworth.
However, while Palace were down, they were not quite out, as Schlupp denied Arsenal a precious clean sheet in the 63rd minute, bundling home from a Michael Olise corner which the Gunners had failed to deal with.
McCarthy's men snapped a four-game scoreless streak with that Schlupp finish, but the Gunners' recent set-piece failings would not come back to bite them this time, as Saka struck his second and Arsenal's fourth with 74 minutes gone.
An attempted clearance from Will Hughes only reached Kieran Tierney, who drilled the ball back in from the left-hand side of the box, and Saka sent a sumptuous first-time finish into the corner beyond Whitworth's reach.
Arteta's side were left untroubled for the remainder of the match as they earned a fresh slice of history, becoming the first team in the English Football League to win nine London derbies in a single season.
The Gunners welcome Leeds United to the Emirates in their first game back following the international break, while Palace - who stay 12th - are at home to Leicester City on April 1.