Wenger claimed some his players were worn out following Thursday's Europa League clash with CSKA Moscow.
Calum Chambers had a great chance to restore the Gunners' lead before the break in very similar fashion to Lacazette's finish, but the full-back could only clip the outside of the right-hand post after stretching to meet Mustafi's header across the box.
It's nearly enough to make Arsenal fans long for the days of Pascal Cygan and Nicklaus Bendtner.
But as they did against Swansea and Bournemouth, the Gunners snatched defeat from the jaws of victory, with Matt Ritchie scoring the victor for Newcastle.
"We can enjoy the win now but then we have to be ready for the next game".
He also becomes the 18th player aged 18 or under to make their league debut for Arsenal under Wenger.
The result sees Arsenal stay sixth and means they are the same number of points - 33 - above bottom-of-the-table West Brom as they are behind leaders Manchester City.
In total, it was their 11th away loss of this disappointing league campaign, and left them five points behind fifth-place Chelsea.
Arsenal have failed to get a point away from home in 2018 having lost all their away fixtures on the road.
After the game, Gunners goalie Petr Cech said the defeat summed up life away from the Emirates Stadium.
It was the away side who emerged the more alert of the two at the start of the second half as they probed for space in between the Newcastle defence.
The decision not to bring in the system next season was made at a recent Premier League shareholders meeting in London, when all 20 member clubs voted.
With Atletico Madrid to face in the semi-finals of the Europa League, Wenger will have to tighten things up at the back.
Newcastle went ahead following a good team play as goal scorer Perez turn provider after he delivered a back-heel to Matt Ritchie who finish off in style in the 68th minute.
His recent form has been insatiable and should the midfield marvel continue to impress on Tyneside, then a place on the plane to Russian Federation for the World Cup this summer may not be out of the question for Shelvey.
- James Comey admits polls were 'a factor' in email announcement
- Everything In The White House Is 'Very Calm And Calculated'
- Binghamton Devils unite to support Humboldt Broncos
- Daniel Ricciardo fires warning to Vettel and Hamilton after Chinese GP win
- Commonwealth Games 2018: Manika Batra- Sathiyan Gnanasekaran bag table tennis mixed bronze
- Russian Federation nerve agent tested BEFORE Skripal attack, damning dossier claims
- Win An Avengers: Infinity War Hamper
- David Ragan posts fastest lap in final Cup practice; Kurt Busch crashes
- PM urges United Nations based resolution over airstrikes
- Bournemouth manager Eddie Howe praises Mohamed Salah