Anthony Stokes climbed off the bench and scored with his first touch to help Sunderland to their fifth win in six games and move them up into fifth spot.
Dwight Yorke came close to an opener when his close-range shot was blocked, while Rory Fallon saw Plymouth's best chance beaten away from 25 yards.
But Stokes lit up a scrappy affair minutes after coming on when he stroked home Dean Whitehead's cross superbly.
And David Connolly wrapped it up from Stern John's pass two minutes later.
606 DEBATE: Give your thoughts on the match
Plymouth Argyle boss Ian Holloway:
"After a very close first half I thought we just folded in the second
half and we were a poor second best to them.
"A lot of credit goes to Sunderland for that but I thought we looked weak out
"That's the first time this season I think that we have come out
Sunderland boss Roy Keane:
"We did the hard work in the first half and in the second half looked even better.
"We've done the job I wanted us to. We've come in, got the result, got the points and are getting back out of here again."
Keane said of goalscorer Anthony Stokes: "It's been a hectic month for Anthony, winning his first international cap and now getting his first goal for us."
Plymouth: McCormick, Connolly, Doumbe, Timar, Capaldi, Norris, Buzsaky (Summerfield 72), Nalis, Halmosi (Sinclair 61), Fallon, Ebanks-Blake (Gallen 72).
Subs Not Used: Sawyer, Gosling.
Sunderland: Fulop, Simpson (Liam Miller 89), Evans, Nosworthy, Collins, Edwards, Whitehead, Yorke, Hysen (Stokes 66), John (Leadbitter 74), Connolly.
Subs Not Used: Carson, Cunningham.
Goals: Stokes 69, Connolly 71.
Ref: K Stroud (Hampshire).