Arsenal were rampant and a fourth arrived in the 35th minute, as Lacazette joined Ramsey in getting a second, finding the bottom-left corner with a smart finish after a well-placed cut-back from the huge Ozil.
Pierre-Emerick Aubameyang is ineligible to play in the competition for Arsenal.
Two minutes after having a goal ruled out for offside, Ramsey finished off a fine team move to net Arsenal's opener in the ninth minute.
Ramsey almost had his hat trick in the 78th minute, only to strike the right post.
Arsenal are certainly warming to the Europa League, collecting their eighth win from 11 games in the competition, scoring 27 times and conceding eight.
The Germany playmaker's chip allowed Ramsey to score the pick of the night's goals, a pirouetting mid-air flick over a stranded Akinfeev that drew gasps from the crowd - closer to full than in recent games, though seemingly still a few thousand short of capacity -when replayed on the big screens.
Wenger confirmed after the game that keeper David Ospina, who suffered an ankle injury on the eve of the game, will be out for between two and three weeks while Mkhitaryan, who was substituted, will miss Sunday's game against Southampton with a damaged knee.
Cristiano Ronaldo's superb overhead kick for Real Madrid against Juventus in the Champions League followed Alex Oxlade-Chamberlain's rocket shot for Liverpool against Manchester City.
MF Aaron Ramsey, 9 - A wonderful performance topped by a goal of the very highest quality.
Ramsey went agonisingly close to getting his coveted third goal 12 minutes from time when he saw a first-time 18-yard strike come back off the right-hand post, but it is unlikely Arsenal will be made to rue that miss as they head to Russian Federation with a commanding lead.
Ahmed Musa nearly put the Russian side ahead immediately after but scuffed his shot, and seven minutes Arsenal were back in front as Lacazette converted a penalty following Georgi Schennikov's foul on Mesut Ozil. In the previous round, the Gunners advanced past AC Milan.
Man of the match - Mesut Ozil (Arsenal)Ozil was at his brilliant best. We did the first part of the job but not the second part.
And, even though the fans' frustrations are abundantly evident, Arsene Wenger is confident that they will come out in force for the game against CSKA Moscow, particularly with so much at stake for the club.
DF Shkodran Mustafi, 5 - While Arsenal excelled at the other end of the pitch, he floundered.
CSKA Moscow, meanwhile, booked their place in the quarter-finals with a hard-earned win over Lyon and they represent a stern challenge for the Premier League side.