Mustapha Bundu curled inside the post to cap a flowing move and put the Pilgrims ahead
Ten-man Plymouth clung on to beat Portsmouth for their first away win of the season and move within three points of safety.
Argyle were good value for the points against the hosts, who had beaten leaders Leeds at the weekend.
Fit-again Ryan Hardie's sublime backheel teed-up Mustapha Bundu to stroke the opener a minute before the break, before Hardie himself doubled the lead four minutes after the turnaround, streaking away from halfway to drill inside the near post.
Plymouth finished the game with 10 men after Matthew Sorinola picked up a second booking in the 86th minute, before Adil Aouchiche lashed what turned out to be a superb consolation three minutes later.
Though the Greens stay bottom, their first win on the road since last April moves them three points from safety, while Pompey remain seven points clear of the drop zone after just their second home defeat in 13 games.
Perhaps unsurprisingly, John Mousinho stuck with the same Portsmouth starting XI from Sunday's excellent 1-0 win over Leeds.
Meanwhile, Argyle boss Miron Muslic made four changes from the dismal 3-0 home defeat by Sheffield Wednesday.
Pligrims top scorer Hardie only came off the bench at half-time on Saturday but started for the first time in six games after a back injury.
Tymoteusz Puchacz, Jordan Houghton and Michael Obafemi – who scored the winner in Argyle's 1-0 win in the reverse fixture in November - also came in for the visitors.
The hosts made a strong start and Freddie Potts glanced a header wide from a Josh Murphy corner inside two minutes.
But from Plymouth's first real attack Hardie's powerful first-time half-volley from the right edge of the area drew a flying save from Sunday's hero Nicolas Schmid in the Pompey goal.
Aouchiche curled narrowly past the top corner at the other end and Andre Dozzell skewed wide from a corner, while Bundu's speculative attempt to catch Schmid off his line from halfway drifted wide.
Just after the half-hour Julio Pleguezuelo slid in to prevent Colby Bishop converting a low cross from Josh Murphy, and from Murphy's subsequent corner Aouchiche's flashing near-post header was somehow clawed off his line by Greens keeper Conor Hazard.
The visitors broke the deadlock when Obafemi's first-time cross from the left was superbly laid off with his heel by Hardie for Bundu to take a touch and stroke to Schmid's left and into the bottom corner – just Argyle's seventh away goal of the campaign.
Pompey started fast after the turnaround and Hazard had to parry away an inswinging Murphy cross-shot.
But the lead was doubled when Marlon Pack was caught out of position and a clearance down the left channel allowed Hardie to streak away from halfway, before stretching to fire low past Schmid's near post.
Cohen Bramall and Liverpool loanee Kaide Gordon were introduced by Mousinho as the hosts shifted formation and upped the tempo and Bishop saw a near-post effort from Zak Swanson's cut-back deflected wide by Nikola Katic on the hour.
Katic inadvertently collided with team-mate Pleguezuelo leading to the Spaniard leaving on a stretcher, with Mumba also coming on to replace Hardie before the restart.
Adil Aouchiche lashed into the top corner to tee-up a grandstand finale with his first Blues goal
Blues sub Mark O'Mahony nodded a perfect Murphy cross past the far post while unmarked inside the final 20 minutes and then came closer with a glancing header from Aouchiche's cross moments later, while Gordon blazed over from distance.
After earlier being booked for time-wasting, Sorinola received a second yellow after bringing down Bramall on the edge of the box and after Murphy's free-kick was blocked, Aouchiche unleashed an unstoppable 20-yard effort through a crowd and into the top corner to raise the roof.
There were 11 minutes added at the end and Bramall saw a shot charged down in the box as the hosts laid siege to the Argyle goal.
But they couldn't find a leveller as Plymouth made it eight unbeaten against the Blues and ended their worst away run in 41 years, which had extended to 20 games without a victory before their trip along the south coast.
'Opportunity spurned' - post-match reaction
Portsmouth manager John Mousinho told BBC Radio Solent:
"I am feeling incredibly disappointed, angry with the performance and disappointed with the opportunity that we've spurned, and how the game has panned out.
"Plymouth came and set up really deep, made it difficult for us. Those are the games where you have to concentrate, not give anything up.
"It's very difficult to do what Plymouth did for 90 minutes but as soon as you give them a goal and then a second goal after half-time, it becomes a lot easier. You get the energy, you can defend the box a bit better.
"We were fine for the first half an hour, we didn't really break them down a lot and then we started to get sloppy. The goal was absolutely abysmal, the second was as well.
"Those are the sort of games that if you can't break sides down, it's difficult to play against and it's a 0-0, you move on.
"We were up for Sunday and we are not good enough to back it up at the moment. In 10 days we have lost to the bottom two sides in the league and beaten the top team."
'The team showed that we are alive' - Muslic
Plymouth coach Miron Muslic told BBC Radio Devon:
"I think it's a big moment for us. After being not capable to win for almost a year finally we rewarded ourselves after a very tough moment against Sheffield Wednesday and after a tough period.
"This team showed again that we are alive and they can count on us.
"That was the spirit we needed, we've actually had it over the past couple of weeks, the only thing we missed was this offensive threat, this transition threat, this goal threat.
"We defended pretty well. Hardie was out for six games and we missed somebody who could run in behind. Tonight we had three players very dangerous in transition. We scored two beautiful transition goals, it all went to plan. I'm very happy.
"It feels brilliant. It was very much needed. When the fourth official told me 11 minutes [added on] I knew we were going to make it."
