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A number of spurned opportunities came back to haunt Arsenal in last week's reverse fixture as Tomas Holes scored late on to cancel out Nicolas Pepe's opener in a 1-1 draw.
But the Gunners were at their efficient best in front of a sparse crowd on Friday (AEST), completely wiping out Slavia's away-goals advantage through strikes from Pepe, Alexandre Lacazette and Bukayo Saka inside 24 minutes.
Slavia had gone 23 games without defeat in all competitions and last lost at home in November 2019, but there was no sign of a comeback as Lacazette added a late fourth for Arsenal to set up a last-four tie with Unai Emery's Villarreal.
Emile Smith Rowe thought he had given Arsenal the lead on the night early on when tapping in after Saka's curler was pushed onto the post by Ondrej Kolar and fell into his path.
The goal was ruled out for offside following a lengthy VAR check, but Smith Rowe played in Pepe a minute later and the winger coolly slotted past Kolar for the visitor's opener.
A second away goal followed from the penalty spot three minutes later, Lacazette sending the keeper the wrong way after Jakub Hromada brought down the lively Saka.
Arsenal showed no signs of slowing as Saka carried the ball inside from the right and drilled a left-footed finish into the bottom-right corner from 18 yards, with Kolar rooted to the spot.
That left Slavia requiring four goals to advance but the Czech champions, who knocked out Leicester City and Rangers en route to this stage, struggled to muster a response.
Lacazette had a penalty appeal rejected when going down in the box but the Frenchman had the last laugh when finding the near post to round off a counter 13 minutes from time, sending Arsenal through with minimal fuss.