After a goalless 45 minutes, the Gunners took the lead five minutes after the restart through Pierre-Emerick Aubameyang's powerful effort before Bukayo Saka doubled the hosts' advantage with a composed finish on the hour mark.
Arsenal completed the scoring as Aubameyang notched his brace to condemn United to a disappointing defeat in North London, extending their winless run in the Premier League to seven matches.
Steve Bruce made eight changes to the side which suffered a 1-0 defeat a Sheffield United and faced an Arsenal side, who beat the Magpies after extra-time in the Emirates FA Cup nine days prior, aiming to extend their unbeaten league run to five matches.
After a quiet opening to the league clash, Aubameyang struck the post for the hosts. As Saka's low cross-cum shot was blocked by Darlow, the loose ball fell into the path of the Gabonese striker but saw his effort from a tight angle clip the inside of the far post.
United's best goalscoring opportunity of the opening half fell to Miguel Almirón as the Paraguayan began a counter-attacking move from inside his own half, eventually picking out Andy Carroll on the left flank before taking the return pass but his attempt at goal flew over the crossbar.
The Gunners wasted another opportunity in front of goal shortly after as Thomas Partey's through ball found Emile Smith Rowe before the 20-year-old teed up Aubameyang, who was unable to hit the target after lifting his first-time effort over the bar.
Arsenal, unbeaten in eight league home games against Newcastle before the evening encounter, went close to netting before the half-time whistle as Aubameyang's intended cross was deflected towards goal by Krafth, forcing Darlow to tip the ball around the post.
In the opening minutes of the second half, Darlow produced a fine stop to deny Lacazette as the Frenchman controlled Saka's cross inside a crowded penalty area before his drilled strike at goal was importantly pushed away by Darlow.
However, Arsenal took the lead in the 50th minute as Aubameyang netted his third successive goal against the Magpies in all competitions.
After Partey picked out the striker with a dangerous pass, the Gabon international drove towards goal before firing past Darlow at his near post into the roof of the net.
Newcastle went in search of an equaliser as Wilson combined with Carroll before the latter, who scored the winner in the Magpies' last away win against the Gunners back in 2010, fizzed an effort wide of the target.
In the 60th minute, Newcastle fell further behind as Smith Rowe advanced beyond Jamaal Lascelles on the left wing before picking out Saka inside the box and the England international produced a simple side-footed finish to double the Gunners' lead.
Darlow was alert to prevent Lacazette from getting on the scoresheet minutes later, blocking the French forward's close-range header after Saka's teasing cross from the right flank.
Arsenal, though, grabbed their third of the night in the 77th minute as Aubameyang tucked the ball into an empty net after Cédric Soares managed to cut the ball from the byline into the striker's path, with the goal standing after a thorough VAR check.
Elliot Anderson, who made his professional debut against Arsenal in the Emirates FA Cup tie nine days ago, was also handed his Premier League bow against the Gunners after his late introduction on an otherwise forgettable evening in the capital.
Newcastle United: Karl Darlow, Emil Krafth, Jamaal Lascelles (c), Ciaran Clark, Jamal Lewis, Matty Longstaff (Jeff Hendrick 79), Jonjo Shelvey, Miguel Almirón (Elliot Anderson 87), Joelinton, Andy Carroll (Jacob Murphy 68), Callum Wilson.
Subs not used: Martin Dúbravka, DeAndre Yedlin, Javier Manquillo, Matt Ritchie, Isaac Hayden, Sean Longstaff.
