Pierre-Emerick Aubameyang ran onto a long ball into the Newcastle area and picked out Lacazette, who stretched to volley home at the far post for his 13th goal of a hard first season following his move from Lyon.
Perhaps encouraged by an Arsenal team sheet showing six changes from the side which had drawn away to CSKA Moscow on Thursday, the Magpies started at a high tempo but soon found themselves forced back into their own half with Lacazette scuffing a fifth-minute shot wide after turning neatly on the edge of the box.
GETTY Paul Merson says Liverpool need to spend big in the summer
"We needed to work had, we didn't in the first half but much more in the second half - defending and playing counter attack against a really good team".
Only two points short of reaching the magical total of 40 for the season, Newcastle responded in the flawless manner and found the equaliser in the 29th-minute when Perez's side-footed DeAndre Yedlin's cross in at Petr Cech's near-post.
Perez delivered a fine finish for the goal, drifting in at the near post to glance home a right-wing cross from DeAndre Yedlin. "Still feel you're capable of finishing above Burnley", - Match of the Day host and former Tottenham striker Gary Lineker fired over a sarcastic tweet as his former rivals sit sixth in the table and just two points above the Clarets.
But it was Newcastle who landed the knockout blow in the 68th minute.
Just to rub it in, Matt Ritchie then sealed the three points in Newcastle's favour when Islam Slimani's headed pass bobbled through to him on the edge of the Arsenal 18-yard box via a Perez flick and the midfielder obliged by clipping home the victor.
Lacazette should have equalised in the closing stages, but he shot into the side-netting.