Nick Powell popped up with a dramatic winning goal with only eight minutes left to send Wigan Athletic back up to second place in League One.
It was almost one-way traffic at the DW Stadium – not for the first time this season – as Latics threw everything at their struggling visitors.
Only a mixture of poor finishing, bad luck and inspired goalkeeping from Kyle Lethern – making his debut – kept Latics at bay until 82 minutes.
But the resistance was finally broken when referee Sebastian Stockbridge whistled for a foul on Michael Jacobs.
And Powell stepped up to smash the ball home from 12 yards.
Even then Latics had to withstand a nervy finale, with Plymouth hitting the bar in stoppage-time through Graham Carey.
But anything other than a home win would have been a total miscarriage of justice, with Latics hitting the bar in the first half through Will Grigg, and seeing the likes of Jacobs, Gavin Massey and Powell thwarted on several occasions by brilliant goalkeeping.
Latics had been boosted by the return of a couple of big players to the starting XI, with Sam Morsy returning from suspension and Grigg restored to the lone striking role.
Ivan Toney dropped to the bench, while David Perkins dropped out of the squad as did Ryan Colclough, despite scoring at Peterborough on Saturday.
Wigan’s attempt to bounce back from only their second league defeat of the campaign was almost off to a flyer when Massey sent over a dangerous cross with only for Powell to head wide.
Plymouth then couldn’t clear a Reece James cross, and Lee Evans’ shot was well saved by Letheren at full stretch.
Powell then had a chance to make amends for his earlier miss when he lined up a free-kick in an identical spot to where he scored from against Bristol Rovers 10 days earlier.
However, this time his shot was dragged wide of the post, to the delight of the couple of hundred Plymouth fans behind the goal who’d made a superhuman effort to travel so far on a Tuesday night.
Latics were awarded another free-kick on the 15-minute mark, with Evans lining this one up.
The initial shot was headed out to the edge of the box to Morsy, who lashed it back towards goal and, via a deflection off Grigg, was unlucky to see it hit the bar and bounce away.
A lightning-fast break from Latics saw Grigg release Massey, whose shot was well saved by Letheren at his near post.
Plymouth couldn’t clear the corner, and some lovely footwork from Dan Burn saw him produce a shot which hit Grigg and rolled harmlessly wide.
Morsy dragged a couple of efforts wide of the post from just outside the area, before Plymouth showed themselves for the first time as an attacking force.
Ryan Edwards might have done better with his header from a Carey corner, which he directed wide of the mark.
Argyle came closer still moments later when Morsy inadvertently played in Lionel Ainsworth, whose close-range shot was brilliantly saved by Jamie Jones at point-blank range. But Latics ended the half on top and a surging run from Jacobs ended with a curling shot that looked destined for the top corner, only to force a fantastic save from Lotheren, who tipped it round the post.
A scramble in the Plymouth box saw Letheren tip over a header Powell header, with the corner seeing an almost carbon-copy, with the goalkeeper again denying Wigan’s top scorer. With Latics committing more and more men forward, they were leaving gaps at the back, and Plymouth substitute Gregg Wylde almost took full advantage on the break.
His shot from the edge of the area took a deflection off Chey Dunkley, and James did well to avoid putting it in at the far post.
Latics then made a double change, with James and Grigg coming off, to be replaced by Callum Elder and Toney. And it almost paid immediate dividends when Nathan Byrne picked out Toney at the far post, only for his header to force a great save from Letheren.
Powell thought he’d opened the scoring inside the last quarter when he was on hand to finish from close range after Massey had seen another effort superbly blocked.
But the celebrations were cut short by the offside flag on the near side.
However, the respite was only temporary for Plymouth, with Powell exacting the perfect revenge after Jacobs had been felled in the box.
It was never going to be a routine last 10 minutes – it never is with Latics – but they were finally able to breathe a huge sigh of relief when Carey’s free-kick flicked the woodwork on the way over.