Having already had their promotion back to the big time confirmed a fortnight ago, Chris Hughton's men made sure it will be them and not West Brom that lifts the trophy - their first since winning the old Second Division under Kevin Keegan in 1993.
Monday night's result also ends Argyle's six-year stay in the second tier, with Sheffield Wednesday and Crystal Palace's final day encounter meaning it is impossible for them to stay up even if they win their remaining two fixtures.
Goals from Andy Carroll and Wayne Routledge were enough to see off Paul Mariner's men, who have paid the price for winning just 11 games all season.
Despite losing their last two matches, Argyle started brightly and nearly went ahead with just 53 seconds on the clock.
Damian Johnson, making his 250th league start, got in round the back and picked out Jamie Mackie, whose drilled effort was beaten away by Steve Harper. Then, from the resulting corner, Bondz N'Gala sent a header over the bar when it looked easier to hit the target.
Newcastle posed hardly any threat in the opening exchanges and had to wait until the 19th minute for their first chance, with Carroll's attempted curler from just inside the area floating harmlessly over.
The striker found his range shortly after, though, opening the scoring with 20 minutes on the clock, rising the highest to connect with Joey Barton's corner and loop a header into the top corner for his 18th goal of the season.
The goal sapped Plymouth of their enthusiasm and the visitors went two goals up eight minutes later.
Barton made it with a defence-splitting pass to Routledge, before the winger coolly rounded David Stockdale and slotted into an empty net.
Mackie then worked Harper again as Plymouth attempted to rally, with Bradley Wright-Phillips and Alan Judge also going close with drives that fizzed just past the goal.
Judge thumped a 35-yard effort against the bar after the break as Newcastle took their foot of the gas, with Hughton taking the opportunity to give £2million signing Leon Best a rare opportunity from the bench.
Plymouth brought on striking prospect Joe Mason in a last-ditch attempt to pep up their attack but, with both sets of fans accepting their respective fates, the standard of play began to deteriorate quickly.
Best nearly put an end to that with 25-yard strike that crashed against the bar, while Stockdale produced a smart save to keep out Barton's close-range hit.
At the other end, Jose Enrique denied Plymouth a late consolation when he cleared Mason's header off the line.