Gregg Wylde and Ryan Brunt struck in three first-half minutes while the latter added another late on to sentence The Stags to their first defeat since they lost at home to Luton on January 23.
Mansfield’s rise up to fourth in the table had been built on an impressive away record but this defeat – only their fifth away from home this term – saw Adam Murray’s side slip to seventh.
With manager Murray sitting in the stands after being hit with a one-match touchline ban following an FA misconduct charge, Mansfield went for broke after the break.
Daniel Alfei was summoned after half-time and the visitors switched to three at the back but by then the damage had been done.
Earlier Brunt wasted a decent opening chance after heading high and wide following an inviting cross by Gary Sawyer.
Mansfield keeper Scott Shearer plunged to his right to tip Craig Tanner’s shot around the post before Argyle took the lead on 33 minutes from the resulting corner.
Mansfield could only partially clear and Curtis Nelson rolled the ball into the path of Wylde to score.
Argyle doubled their lead three minutes later after Peter Hartley was wrestled to the floor by Krystian Pearce and the referee pointed to the spot and Brunt fired into the bottom left corner.
Plymouth piled on the pressure and Jordan Forster headed Graham Carey’s cross against the post.
Ryan Tafazolli, who had earlier hit the post, watched on as his 53rd minute header appeared to be going in until Brunt diverted the ball on to the crossbar.
Shearer prevented further damage after racing off his line to deny Oscar Threlkeld and the Mansfield keeper pulled off a stunning save from Wylde.
But he was powerless as Brunt poured further salt into Mansfield wounds when he tapped home in the 84th minute.