Nick Chadwick scored the winner as Sunderland slumped to a third straight Championship defeat under Niall Quinn.
Quinn is still searching for his first win as Sunderland boss
The visitors had to come from behind after Daryl Murphy scored from a tight angle on one minute, and it was David Norris who levelled with a superb lob.
Plymouth went ahead when Barry Hayles punished Kenny Cunningham for a poor backpass but Sunderland hit back after the break with a Stephen Elliot header.
Then on 82 minutes Chadwick sealed the points when he struck with a low shot.
Sunderland's hesitancy in defence which preceded Chadwick's decisive strike was on show for most of the game.
The Black Cats were hardly helped when Clive Clarke's debut ended prematurely in the 20th minute as he exited holding his groin.
Hayles and Norris should have both notched more than once but neither could finish off chances when one-on-one with keeper Ben Alnwick.
Sunderland's Chris Brown headed against the bar in the 66th minute - it would have put the home side 3-2 up, but instead the Black Cats proved all out of luck again.
Sunderland manager Niall Quinn
"I'm very disappointed. It's a game we should have won.
"It was a wonderful chance to get going and turn a corner, but it was awful at times and we lacked bottle to take the situation by the scruff of the neck.
"The players have to take on responsibility and as a unit we didn't do that. Everyone and his dog knows we have to strengthen the squad."
Plymouth manager Ian Holloway
"Obviously I haven't been here long but I'm enjoying every minute.
"The boys have fantastic spirit. I'm very proud.
"I said at half-time that I wouldn't want to be in the other dressing room. The fans weren't happy and there was a lot of negativity out there."
Sunderland: Alnwick, Delap, Cunningham, Clarke (Wright 20), Danny Collins, Lawrence (Stead 58), Whitehead, Leadbitter, Miller (Brown 63), Stephen Elliott, Murphy.
Subs Not Used: Ward, Neill Collins.
Goals: Murphy 1, Stephen Elliott 67.
Plymouth: McCormick, Connolly, Doumbe, Aljofree, Capaldi, Norris, Wotton, Summerfield (Buzsaky 72), Hodges, Hayles, Ebanks-Blake (Chadwick 71).
Subs Not Used: Sawyer, Reid, Djordjic.
Goals: Norris 8, Hayles 39, Chadwick 82.
Ref: R Olivier (W Midlands).