Harvey Barnes' fine finish fired the Magpies into an early lead at an electric Stade Vélodrome, the in-form winger's sixth goal in his last eight competitive matches, before Aubameyang's clinical finish from a tight angle levelled the league phase clash inside the opening minute of the restart.
Targeting a fourth consecutive Champions league win for the first time in the club's history, Newcastle were dealt a further blow in quick succession as Aubameyang netted the eventual match-winner, turning the ball home from Timothy Weah's cross as Newcastle were, ultimately, edged out in France.
Eddie Howe made three changes from the side which claimed a 2-1 win against Manchester City last weekend, with Anthony Gordon returning from injury in place of Nick Woltemade while Joe Willock and Dan Burn replaced Joelinton and Lewis Hall respectively.
The Magpies began the league phase clash in strong fashion as Malick Thiaw went agonisingly close to scoring his first United goal since joining from AC Milan last summer, rising high from a free-kick before the German's looping header was hacked off the line by Pierre-Emile Højbjerg.
Newcastle took the lead inside six minutes as Barnes netted his seventh goal of the season in all competitions. After Sandro Tonali latched onto Willock's pass, the Italian midfielder's cross was flicked into Barnes' path by Anthony Gordon before the former cooly slotted the ball into the bottom right-hand corner.
Nick Pope produced a key stop to deny Aubameyang from levelling for the hosts as the Gabon international raced in behind the United defence but saw his effort from a tight angle blocked by the United goalkeeper's strong right arm.
Pope was alert shortly after to deny Aubameyang once more, impressively pushing the Marseille striker's fierce half volley out for a corner.
Tonali was unable to double Newcastle's lead as the 25-year-old raced onto Bruno Guimarães' neat pass and, after his initial cross was only cleared back into the midfielder's path, his low strike at goal was held by Marseille goalkeeper Gerónimo Rulli.
Newcastle survived numerous goalscoring opportunities from the hosts, with Igor Paixão curling a dangerous effort from the edge of the box wide of the right-hand post before Aubameyang glanced a close-range header wide of the target following Mason Greenwood's inviting cross from the right flank.
Aubameyang continued to cause a threat to the United backline, latching onto the ball towards the edge of the box after Tonali lost possession but Thiaw recovered strongly to put off the striker, despite the African forward managing to fire a sliding effort wide of the right-hand post.
Gordon was unable to net his fifth Champions League goal of the 2025/26 campaign after collecting Willock's pass and driving into the box before his low shot at goal was clawed away by Rulli, with the loose ball cleared from the box.
Newcastle found themselves on level terms within the opening 60 seconds of the second-half as Aubameyang equalised for the Ligue 1 outfit, racing onto Darryl Bakola's pass and, after rounding the incoming Pope from distance, placed a clinical effort from a tight angle into an empty net.
The Magpies thought they had regained their one-goal cushion two minutes later as Barnes turned the ball into an empty net from Willock's cross towards the back post but the goal was disallowed after Barnes had strayed into an offside position.
The visitors were dealt a further blow in the 50th minute as Aubameyang netted his and Marseille's second goal of the night, with the veteran forward getting onto the end of Weah's dangerous cross from the right flank before directing a near-post finish into the roof of the net.
Newcastle withstood further attacking pressure as the French outfit broke with pace along the left flank before Greenwood's drilled effort was saved by Pope at his near post.
Seeking an equaliser, Willock was unable to net his first Champions League goal as the London-born midfielder collected Guimarães' teasing pass inside the box but saw a fizzing effort turned out for a corner by Rulli.
Anthony Elanga, introduced from the substitutes' bench, almost made a swift impact after being fed by fellow substitute Nick Woltemade inside the box but saw his powerful effort pushed around the post by Rulli's fingertips.
Despite five minutes of stoppage-time, Newcastle were unable to net an all-important equaliser as their three-game winning streak in the competition came to an end but, despite the defeat, remain in the top eight of the Champions League standings before Wednesday evening's fixtures.
Newcastle United: Nick Pope, Fabian Schär (Anthony Elanga 60), Sandro Tonali, Anthony Gordon (Nick Woltemade 72), Harvey Barnes, Malick Thiaw, Tino Livramento (Lewis Hall 60), Jacob Murphy (Lewis Miley 60), Joe Willock (Jacob Ramsey 72), Dan Burn, Bruno Guimarães (c).
Subs not used: Max Thompson, Aaron Ramsdale, Sven Botman, Joelinton, Alex Murphy, Sam Alabi.
