Rhys Oates put the Stags ahead in the 22nd minute, but the hosts soon equalised through James Wilson’s strike and clinched the win through substitute Kian Harratt’s late double.
The result sees Nigel Clough’s fall below their opponents into 10th place, four points shy of the last play-off place which is currently occupied by Bristol Rovers.
It was the first time Stags had lost back to back league games since 11th September.
Clough made four changes to the side that started the agonising defeat against Tranmere on Friday, with Lucas Akins and Stephen Quinn both missing out through injury and Newcastle loanee Matty Longstaff sidelined as well.
Farrend Rawson was also a doubt with a head injury but managed to make the starting 11 as Mansfield looked to bounce back from their 14-match unbeaten run being brought to an end.
James Perch made his first start since his fractured skull and Ollie Clarke, Kieran Wallace and George Lapslie also came into the starting XI with Clarke captaining the side.
John-Joe O'Toole was back on the bench following his three-game suspension.
There was little action to note in the opening 20 minutes and it was the first shot of the match that saw Oates open the scoring to the delight of almost 1,000 travelling fans.
The 27-year-old shrugged off his marker to latch onto a ball over the top from Kieran Wallace and he showed great composure to round goalkeeper Aidan Stone – who signed for Port Vale from Mansfield last summer – and place the ball into a gaping goal on 22 minutes.
However, the hosts responded well and grabbed the equaliser 11 minutes later thanks to Wilson, who having been slipped through by Ben Garrity burst away from the Mansfield defence and struck the ball across and under the dive of goalkeeper Nathan Bishop and into the bottom right corner which the keeper will have been disappointed with.
Mansfield came close to re-taking the lead just before the hour-mark when Jamie Murphy's effort was well saved by Stone who then made another superb stop from close range to deny George Lapslie, who looked a certain scorer after an excellent move.
Stags were soon made to pay for that as substitute Harratt pounced onto a header back into the area from Vale captain Tom Pett before seeing his shot saved by Bishop and volleying home the rebound on 76 minutes.
Nathan Smith came close to equalising as he sliced Lapslie’s driven ball onto his own crossbar before Harratt punished them again minutes later as he made it a brace from the bench with two minutes to go.
PORT VALE: Stone, Smith, Martin, Hall, Worrall, Garrity, Pett, Charsley (Walker, 69), Hussey (Benning, 67), Wilson (Harratt, 72), Proctor. SUBS NOT USED: Holy, Amoo, Edmondson, Cooper.
STAGS: Bishop, Perch, Rawson, Hawkins, McLaughlin (Bowery, 87), Stirk, Clarke (O’Toole, 57), Murphy, Lapslie, Wallace, Oates (Johnson, 80). SUBS NOT USED: Hewitt, Marris, Stech, Law.
REFEREE: Peter Wright.