The second half was a much tighter affair but it was the Magpies who got the victor in the 68th minute when Matt Ricthie calmly slotted home from close range to seal all three points for Rafael Benítez's men.
In terms of the game itself, it began at a slow pace as both teams wanted to see how each other were going to approach the game and that caused the Magpies a problem as the Gunners took the lead with their first real attack of the game.
Arsene Wenger, whose primary focus is on the Europa League, started Lacazette and Pierre-Emerick Aubameyang together for the first time and the duo combined to break the deadlock 14 minutes in at St. James' Park.
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Calum Chambers should have put Arsenal back in front towards the end of the half, but he pushed an attempt wide as he slid in to meet Mustafi's header.
Ritchie, though stunned the Gunners with a second goal for Newcastle with 68 minutes played, as he smashed home past Cech, having picked up a Perez flick as Nacho Monreal's poor headed clearance fell for second-half substitute Islam Slimani, who nodded the ball down to the goalscorer.
Kenedy, on loan from Chelsea, came close to putting the result beyond doubt with a looping effort that hit the crossbar with Cech beaten.
Wow! Quite a few changes there!
And that's how it finished: with Newcastle safe and sound in 10th place on 41 points and Arsenal - the only team left in England's top five divisions still to win a point away from home in 2018 - left teetering in sixth, two points above Burnley.