Plymouth's Gregg Wylde fired in the opener with a stunning volley from outside the box past Scott Shearer.
Ryan Brunt doubled the advantage from the penalty spot after Peter Hartley was fouled by Krystian Pearce.
Mansfield's Ryan Tafazolli hit the post with a header, before Brunt completed the scoring when he deftly turned Jake Jervis' cross into the far corner.
Plymouth Argyle kept their League Two promotion hopes on track with a convincing win over Mansfield Town.