Gabriel Martinelli opened the scoring in the first half at the Emirates Stadium to put the leaders on course for a sixth successive league victory.
It was redemption for Martinelli, whose missed penalty condemned Arsenal to Europa League last 16 defeat in their shoot-out against Sporting Lisbon on Thursday.
Mikel Arteta’s side needed just 45 minutes against struggling Palace to erase the bitter taste of that loss.
Saka followed Martinelli’s goal by doubling Arsenal’s lead before half-time.
Granit Xhaka netted the third after the interval and Jeff Schlupp’s reply was no consolation as the influential Saka’s second capped Arsenal’s stylish display.
Arsenal now have a substantial eight-point lead over second placed Manchester City, who took the weekend off from Premier League duty to thrash Burnley in the FA Cup quarter-finals on Saturday.
With a game in hand on Arsenal and a crucial clash with the Gunners looming on April 26, Pep Guardiola’s champions will still believe they can win a fifth title in six seasons.
But heading into the international break, Arsenal have ensured the fate of the title race will be in their hands in the final 10 games.
After surrendering top spot with a defeat against City in February, Arsenal have responded impressively, showing a maturity and composure far beyond the Gunners’ teams that routinely underachieved in recent years.
Arteta deserves immense credit for transforming a side that blew their top four place last season.
Less than a year later, Arsenal, the first English side ever to win nine London derbies in a single season, have the look of champions elect.
Arteta had labelled the Palace clash as the most important match of his managerial career and his players once again rose to the challenge.
Arsenal played a gruelling 120 minutes against Sporting before their Europa League campaign ended in painful fashion.
Such a quick turnaround could have tested Arsenal mentality and physically.
But they had the ideal opponents in a Palace team now without a win in their 13 matches in 2023 and reeling from Friday’s sacking of boss Patrick Vieira.
Vieira was a key member of the last title-winning Arsenal side 19 years ago and Gunners fans chanted his name throughout the game.
Arteta had described Arsenal’s run-in as “11 finals” and he made six changes to freshen up his team for the first of those hurdles.
Palace, led by interim boss Paddy McCarthy, nearly took a shock lead when Wilfried Zaha’s shot hit the post, deflected off diving Arsenal keeper Aaron Ramsdale and rebounded just wide.
That served as a wake-up call for Arsenal and they made the breakthrough in the 28th minute.
Saka wriggled free in the penalty area to collect Ben White’s pass and pulled his cross back to Martinelli.
The Brazilian forward took a clever touch to elude Joel Ward before driving a clinical finish past Joe Whitworth from 12 yards for his sixth goal in his last eight appearances.
Saka ensured Arsenal’s relentless pressure paid dividends again in the 43rd minute.
He played the ball back to White and his return pass was perfectly weighted for the England forward, who planted a cool finish into the far corner from close-range.
Arsenal were rampant and Xhaka put the result beyond doubt in the 55th minute.
A sumptuous exchange of passes around the Palace area left the visitors bewildered before Xhaka applied a deft finishing touch to Leandro Trossard’s through-ball.
Schlupp stabbed in Palace’s first league goal in nearly seven hours after Arsenal failed to clear a 63rd minute corner.
But Saka had the last word with his 13th goal this season, a fine first-time finish from Kieran Tierney’s 74th minute pass.