Leeds striker Mark Viduka was dropped from Leeds' starting line-up due to a "lack of discipline", so Michael Bridges made his first Premiership start since December.
Brazil defender Roque Junior and Lamine Sakho were the other two changes from last weekend's 3-1 defeat to Liverpool, replacing Dominic Matteo (injured) and James Milner, who dropped to the bench.
Thierry Henry hit two of Arsenal's four goals and was only denied a hat-trick when team-mate Ray Parlour inadvertently blocked a goalbound shot from the magnificent Frenchman.
Robert Pires and Gilberto were also on the mark, and although Alan Smith netted a consolation effort, Leeds were ruthlessly outclassed as they fell to a fourth successive defeat in league and cup.
The ruthless Gunners were three goals up in the opening 32 minutes.
Sakho was in the action early on, shooting straight at goalkeeper Jens Lehmann from the edge of the penalty area and, although in an offside position, screwing another effort wide.
With eight minutes gone Ashley Cole's ball out of defence sent Henry sprinting into the penalty box and he expertly directed his low shot just inside the far post.
Nine minutes later Arsenal doubled their lead. Freddie Ljungberg cut in from the right, Leeds failed to cut out the cross and Pires was left unmarked beyond the far post to slide the ball past Paul Robinson.
David Batty committed a succession of fouls and his frustration led needlessly to a booking for dissent in the 28th minute.
Henry scored his second and Arsenal's third in the 32nd minute. Dennis Bergkamp took a sublime return pass from Ray Parlour and when Bergkamp's shot thudded back off a post, Henry calmly stroked it in from eight yards.
Leeds began the second half with James Milner in place of Bridges, but Arsenal grabbed their fourth in the 51st minute.
Salomon Olembe fouled Ljungberg on Leeds' left, Bergkamp sent a deep free-kick to Pires and he cut back for Gilberto to drill home from 15 yards.
The service to the Leeds forwards did not improve and the Sakho was soon replaced by Aaron Lennon on the hour.
The youngster had an immediate impact as two minutes after his arrival his left-wing cross produced a goal out of the blue as Smith stabbed home for his fourth of the season.
Then Smith hit a low shot hit a low shot against the post, although a linesman's flag prevented the chasing pack capitalising.
Edu, a 70th-minute substitute for Ljungberg, drove through the midfield in the 78th minute but when the ball finally fell to Henry his perfectly-placed shot was destined for goal when it hit Parlour and bounced to safety.
It could have been a lot worse for The Whites!