Peter Halmosi and Sylvain Ebanks-Blake were on target as Plymouth sealed a fifth successive victory.
Hull, free from relegation danger, were caught on the counter as Damien Delaney fouled David Norris, but Ebanks-Blake's penalty was kept out by Boaz Myhill.
But in injury time, Norris crossed for Halmosi to loop in from close range.
After the break, a Halmosi cross was fiercely volleyed in by Ebanks-Blake but Hull hit back and substitute Stuart Elliott tapped in a loose ball.
Hull City manager Phil Brown:
"If we had equalised in the last minute that would have summed our season up. We've been testing ourselves all season and then stepping up to the plate.
"We know what's needed to win football games and we've proved that. But there's been some great highs but also some low lows.
"But the challenge was to be fourth bottom and still a Championship team and we've succeeded in both of them. Hopefully by Wednesday or Thursday I'll have an idea who wants to be with us and who wants to be away - I expect a busy summer."
Plymouth Argyle boss Ian Holloway:
"I'm very pleased to win the game and what we are changing into.
"We were very accomplished and calm and now understand the league and how to win games in it. Considering how many young players we've got, I'm delighted.
"Our cup run spoiled our momentum and we didn't deserve to be down there (in
11th place). But it shows the character of the lads to win their last five games. Hopefully we can build on that, move on and get better - we want to move forward."
Hull: Myhill, Doyle, Turner, Delaney, Dawson, Parlour (Peltier 51), Ashbee, Marney (Featherstone 75), Forster, Windass, McPhee (Elliott 57).
Subs Not Used: Duke, Coles.
Booked: Ashbee, Doyle.
Goals: Elliott 61.
Plymouth: Larrieu, Connolly, Doumbe, Seip, Sawyer, Halmosi (Gallen 85), Nalis, Norris, Buzsaky, Ebanks-Blake, Hayles (Fallon 90).
Subs Not Used: McCormick, Timar, Djordjic.
Booked: Connolly.
Goals: Halmosi 45, Ebanks-Blake 59.
Att: 20,661
Ref: S Tanner (Somerset).