Richard Chaplow hit an injury-time equaliser to complete Preston's comeback and end Plymouth's slim hopes of a play-off place.
Jamie Mackie opened the scoring from well outside the area with a shot which flew into the net via a deflection.
Argyle doubled their lead from the spot, with Paul Wotton firing in after Krisztian Timar was upended.
But Neil Mellor struck from eight yards before Chaplow also pounced from close range in the dying stages.
Plymouth manager Paul Sturrock:
"I am gutted that we are not in the play-off hunt any more but as it was Crystal Palace have won anyway and they are in the box seat.
"Now what we have got to do is make sure that we achieve our highest finish ever in this league.
"Previously that was last season, when we were 11th. At this moment we are 10th and I would like to think that we can get three points at home next week (to Blackpool) and then maybe scramble up some places."
Preston manager Alan Irvine:
"We tried all sorts of different attacking options and really just threw everyone forward. We had nothing to lose, being 2-0 down made my decision easy.
"We remember what happened at Queens Park Rangers, when we conceded two goals in the last minutes, so we know it's always possible and this time it was us getting the last minute goal.
"My job when I came in was trying to get us to safety and we've managed to do that now.
"Obviously I am delighted about that and hopefully it gives us the chance to do some work during the summer to get us up at the other end of the table next season, going for promotion rather than fighting relegation."
Plymouth: McCormick, Connolly, Anderson, Timar, Paterson, Mackie (Teale 90), Wotton, Abdou, Halmosi (Nalis 81), MacLean (Easter 63), Fallon.
Subs Not Used: Doumbe, Summerfield.
Booked: Timar.
Goals: Mackie 12, Wotton 75 pen.
Preston: Lonergan, Jones, Mawene, St. Ledger (Trotman 31), Davidson, Sedgwick (Carter 89), McKenna, Chaplow, Lewis Neal (Whaley 75), Mellor, Hawley.
Subs Not Used: Chris Neal, Hill.
Booked: Sedgwick, Mawene, Mellor.
Goals: Mellor 77, Chaplow 90.
Att: 10,727.
Ref: Andy Penn (W Midlands).
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