It was only the fourth time that a team top of the Premier League had been eliminated from the FA Cup by a lower division club.
Now Liverpool must shake off the embarrassment of their miserable trip to the west country in time for the last Merseyside derby at Goodison Park against Everton on Thursday.
There is little need for Liverpool to panic as a win over Everton would move them nine points clear of second-placed Arsenal in the title race.
The Reds are also through to the Champions League last 16 and will face Newcastle in the League Cup final in March.
Masterminding a famous victory over Liverpool while fighting to haul Plymouth off the bottom of the Championship was no hardship for Argyle manager Miron Muslic, who was a refugee from war-torn Bosnia as a child.
Muslic – hired by Plymouth to replace the sacked Wayne Rooney in January – was forced to move to Austria aged 9 after escaping his home town of Bihac after it fell under siege by Serbian forces in 1992.
Plymouth had already beaten Premier League side Brentford in the third round, but their victory against West Brom last weekend was their first in the league since November.
In the circumstances, Plymouth’s superb performance will rank as one of the FA Cup’s greatest giant-killings.
Liverpool misery
Under a wintry sun by the Devon coast, Liverpool’s under-strength line-up got even weaker when Joe Gomez limped off injured early in the first half.
Liverpool struggled to find any momentum as gritty Plymouth worked tirelessly to keep them at bay.
It took until the 36th minute for Liverpool to muster a shot on target when James McConnell’s long-range drive was repelled by Conor Hazard.
Slot wore an exasperated expression that summed up Liverpool’s lethargy even before Darko Gyabi’s overhead kick was blocked by Harvey Elliott’s raised arm in the 54th minute.
It was a clear penalty and Hardie kept his composure to send Caoimhin Kelleher the wrong way from the spot.
Diogo Jota and Darwin Nunez were denied by fine saves from Hazard in stoppage-time as Home Park erupted in celebration of an astonishing result.
Wolverhampton Wanderers cruised into the fifth round as two goals in the space of 39 seconds sealed a 2-0 win at second-tier Blackburn Rovers.
Languishing just two points above the bottom three in the English top flight, Vitor Pereira’s side took a welcome break from the fight to avoid Premier League relegation.
Wolves, who haven’t been to the FA Cup final since they last won the competition in 1960, went ahead in the 33rd minute when Joao Gomes’ shot beat Balazs Toth’s weak attempted save.
Less than a minute later, Wolves netted again as Nelson Semedo’s pass sent Matheus Cunha racing clear and the Brazilian forward’s blistering strike whistled into the far corner.
Under-fire Tottenham boss Ange Postecoglou cannot afford another cup exit when his team visit Aston Villa in the late match.
Postecoglou boasted earlier this season that he always wins a trophy in his second campaign, but the Australian’s options to achieve that target will be dwindling if Villa knock them out.
