Two goals from Gabriel Martinelli and Bukayo Saka's deflected strike put the Gunners 3-0 up before half-time.
Raphinha's penalty pulled a goal back, but Emile Smith Rowe rounded off a miserable week for Leeds after their 7-0 thrashing at Manchester City on Tuesday.
Leeds boss Marcelo Bielsa described his side's performance at the Etihad in midweek as the worst in his four years in charge and there was no sign of any improvement from his injury-hit squad.
The Elland Road crowd remained behind the Argentine as they chanted his name in the closing stages.
Bielsa was without England internationals Kalvin Phillips and Patrick Bamford, captain Liam Cooper and Spain forward Rodrigo amid an injury crisis that saw 15-year-old Archie Gray earn a spot on the bench.
Arsenal moved into the top four for the first time in more than a year with victory over West Ham on Wednesday and opened up a four-point gap on the chasing pack for a place in next season's Champions League.
Pierre-Emerick Aubameyang was absent once more for the Gunners after being stripped of the captaincy by Mikel Arteta for a disciplinary breach.
His absence has given Martinelli the chance of a consistent run of Premier League starts for the first time since the bright start to his Arsenal career was interrupted by a series knee injury in June 2020.
The Brazilian has scored four times in his last six games as Arsenal.
If not for goalkeeper Illan Meslier, Leeds could have been on the end of a similar beating to the one they suffered against City as the Frenchman made excellent saves from Alexandre Lacazette and Thomas Partey inside the first five minutes.
Meslier was helpless for the opener when Lacazette robbed Adam Foreshaw inside the Leeds box and Martinelli slotted the loose ball into the top corner.
The 20-year-old showed his pace and poise in front of goal to double Arsenal's lead with a dink over Meslier from Granit Xhaka's pinpoint pass on 28 minutes.
Meslier was forced into another fine save from Kieran Tierney while at the other end Leeds' star man Raphinha missed a glorious chance to pull a goal back by firing wide with just the goalkeeper to beat.
Instead, Leeds had a three-goal deficit to overcome at half-time after Saka's deflected shot left Meslier wrong-footed three minutes before the break.
The hosts at least showed some spirit in the second period and should have been playing against 10 men when Xhaka escaped a red card for a stamp on Raphinha's ankle.
The Brazilian, who has now has scored eight of Leeds' 18 goals this season, fired home a penalty into the top corner after Joe Gelhardt had been brought down by Ben White 15 minutes from time.
Arsenal have blown the lead in their last two away league games at Manchester United and Everton, but there was no collapse this time.
Substitute Smith Rowe rounded off the scoring as he blasted home Martin Odegaard's precise pass.
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