A double from Bradley Wright-Phillips helped Argyle stretch their unbeaten run in league Devon derbies to 13 against an under-par and illness-hit Exeter City.
League One's top goalscorer opened the scoring just before the half-hour with a simple finish into an empty net after Artur Krysiak dropped a cross under pressure.
City looked for a way back into the game, Jamie Cureton coming close on the stroke of half-time and Troy Archibald-Henville had a decent penalty claim waved away.
But the former Southampton man grabbed his second on 57 minutes, heading home Craig Noone's pinpoint cross to make it an unhappy return to Home Park for Paul Tisdale's men.
The manager himself had been suffering with flu during the week along with some of his coaching staff and players, most notably Steve Tully and Ryan Harley.
Tully wasn't named in the squad while Harley was a second half substitute. Those absentees meant a change in set-up and personnel from the 3-3 draw at Oldham 18 days ago.
Richard Duffy was the right-back in a back four along with Matt Taylor, Troy and Scott Golbourne. David Noble replaced under the weather Harley in midfield alongside James Dunne and the impressive Liam Sercombe while Dan Nardiello, Richard Logan and Cureton were up front.
After the huge build-up and anticipation the game failed to spark into life early on. For the Grecians, Noble was getting plenty of the ball while Taylor was the victim of a crunching tackle from Connor Clifford.
Noble was then very close to sending Golbourne in with a clever throughball before Troy headed City's first real chance over the bar from Sercombe's corner.
The former Spurs man was then called upon at the other end and he came out on top as the last man in a race against Joe Mason.
Then the goal came and triggered the game into life. Noone won a free kick which he then sent into the box. It was caught by the rising Krysiak. But as he landed with the ball it seemed to bobble out of his grasp, leaving Wright-Phillips with a simple lobbed finish.
Many behind the goal cried 'foul' and their misery was compounded by the jubilant Argyle players celebrating in front of them.
The Pole looked as frustrated as any by the goal but he didn't switch off and he took a cross superbly minutes later with Mason lurking.
Former Grecian loanee Noone was involved in most of Plymouth's good moves and he fired a shot wide shortly after from Wright-Phillips's pass.
On 31 minutes Cureton shot a tame effort straight at David Button after he'd latched onto Dunne's pass and spun on the edge of the box.
The keeper, on loan from Spurs, then claimed a knock-down from Logan meant for Cureton as City begun to create more chances. The best of these came on the stroke of half-time when, following a bit of penalty-area pinball, Logan fed Cureton again but the former Norwich man pulled his shot from an angle inches wide of the far post with the goal gaping.
After the break Logan headed wide and Troy felt he was held inside the box as City looked for a second half improvement. But he was then a relieved man at the other end when a cross seemed to take a nick off him and almost found its way into the net.
Noone and Cureton both had half-chances before the home side doubled their lead, with the diminutive winger again involved. Noone whipped a cross in from the left hand flank that was headed home from the dead centre of goal by Wright-Phillips.
After substitute Carl Fletcher smashed a pile-driver over the bar Tisdale rung the changes, sending on Harley and Billy Jones for Logan and captain Taylor.
Harley had been sorely missed and we saw just a bit of the magic the under-the-weather playmaker is capable of shortly after his introduction, it's just a shame his right-footed free kick curled the wrong side of the post.
Nardiello then made way for the hard-working John O'Flynn as City looked for a way back into the game with time running out.
Duffy had to hack the ball off the line and at the other end Golbourne's left-footed thunderbolt flew inches wide. Harley then showed good feet but couldn't test Button with his shot.
Sercombe's toepunt right at the keeper in the dying minutes was the best City could muster and there was no repeat of the majestic comeback seen during their last League One outing all those weeks ago.
Plus points? Argyle are still one point and two places below us in the table and we have a chance to make the Area Final of the JPT on Tuesday night against a Rovers team hammered 6-2 this afternoon by Saturday's opponents Sheffield Wednesday.