Reds boss Arne Slot's decision to rotate through ten different players from their last game, victory over Tottenham in the Carabao Cup semifinal, backfired as Plymouth were worthy of this fourth round boilover.
The winner came from the spot as Ryan Hardie kept his cool to convert a penalty awarded for a hand-ball against Liverpool midfielder Harvey Elliott.
Forcing the penalty was Plymouth's outstanding attacker on the day, Darko Gyabi, who was a handful for Liverpool's defence throughout the tie.
Hardie soon after had a shot turned onto the post by Liverpool keeper Caiomhin Kelleher.
At the other end, Plymouth keeper Conor Hazard produced a superb save late on to deny Darwin Nunez an equaliser. From the resulting corner, Kelleher was able to connect with a header, but it went wide before the final whistle was blown.
Making the result all the more remarkable was that this win was Plymouth's first in three months.