The young Magpies, requiring a win to keep their hopes of progressing into the knockout stages alive, fell behind in the first-half following Lucas Akins' volley before Ben Quinn's slotted finish doubled the Stags' lead before the half-hour mark.
Quinn's impressive second-half strike extended the League One side's further before Newcastle striker Ben Parkinson was denied from the penalty spot in the final minutes of the Northern Section Group H clash.
Diarmuid O'Carroll made five changes from Saturday's Premier League 2 defeat against Manchester United as Australia international Garang Kuol, the youngest player to play in a FIFA World Cup knockout match since Pelé in 1958, was handed his first start for the Magpies' under-21 side since agreeing to join United from Central Coast Mariners in January 2023.
Newcastle's youngsters fell behind in the 14th minute through Akins' volley as the Grenada international latched onto Ben Quinn's cross from the left flank before slamming a powerful first-time effort into the net.
Kuol, who spent the duration of the 2023/24 campaign on loan at Dutch outfit FC Volendam, went close to netting on his maiden outing for United's under-21 side as the 20-year-old forward combined neatly with Hernes before the Cairo-born youngster's close-range shot from a tight angle was blocked by Flinders.
Hernes, who joined the Magpies from Shrewsbury Town in September 2023, went close to drawing the visitors level after an attacking move involving Kuol and Parkinson saw the latter pick out Hernes inside the box but the Norway Under-20 international's first-time strike was directed over the crossbar.
In the 29th minute, Newcastle were dealt a tough blow as Mansfield extended their advantage through Flint as the Irish teenager collected Frazer Blake-Tracey's pass inside the box before calmly slotting the ball near the front post.
United, however, were unable to halve the deficit before the half-time break but continued to threaten the Stags backline, with Johnny Emerson's fierce cross-cum shot forcing Flinders to turn the ball over his own crossbar before Kuol was played through on goal minutes later by Jay Turner-Cooke but his tame effort was held by the Stags shot-stopper.
Parkinson, who made his Premier League debut for the Magpies away at AFC Bournemouth in November 2023, was unable to net his sixth goal of the season at under-21 level shortly after the restart as the Durham-born teenager raced onto Turner-Cooke's neat pass but was denied a shot at goal following Alfie Kilgour's last-ditch sliding tackle.
Trevan Sanusi, introduced at the restart, went close to netting his first goal of the 2024/25 season at second-string level as the Birmingham-born winger, who made his Magpies first-team debut during a pre-season friendly win against Hull City last summer, darted in from the left flank before his bending effort flew wide of the right-hand post.
In the 69th minute, Newcastle conceded a third as Quinn grabbed his second goal of the night, cutting inside before firing a strike from the edge of the penalty area into the roof of the net.
Teenage striker Sean Neave, who signed his first professional contract last summer, went close to netting his first goal at under-21 level as the 17-year-old striker, who scored seven goals in his last four league games at under-18 level, saw a fierce volley from Turner-Cooke's lofted pass beaten away by Flinders.
With the full-time whistle approaching, Newcastle were awarded a penalty after Neave was bundled over inside a crowded penalty area but Parkinson was denied a sixth goal in his last seven away games at under-21 level as the versatile forward's resulting attempt from 12 yards was parried by Flinders before the loose ball was hooked out for a corner.
Newcastle United Under-21s: Aidan Harris, Leo Shahar, Cathal Heffernan (c), Charlie McArthur, Dylan Charlton, Travis Hernes, James Huntley (Anthony Munda 61), Jay Turner-Cooke, Johnny Emerson (Trevan Sanusi 46), Garang Kuol (Sean Neave 61), Ben Parkinson.
Subs not used: Adam Harrison, Alfie Harrison, Josh Donaldson, Harry Powell.
