Simon Haworth's 17th goal of the season just before the hour kept Tranmere's promotion hopes alive and at the same time dealt Plymouth's a hefty blow.
Haworth headed home in front of the Merseysiders' travelling fans to inflict a second home defeat in three games on the Pilgrims.
Plymouth manager Paul Sturrock made one enforced change to the side that won 1-0 at Oldham seven days previously with Marino Keith's back injury relegating him to the bench, swapping places with Ian Stonebridge.
Tranmere surprisingly omitted Mickey Mellon, captain in last week's home defeat by Swindon, his place going to Tyrone Loran.
The visitors had the best of a disjointed first half, with Canadian international Iain Hume going close after winning a one-on-one with Argyle goalkeeper Romain Larrieu. Only David Worrell's last-gasp intervention kept the ball out.
Tranmere defender Ian Sharps then headed Shane Nicholson's free-kick wide when well placed, before Plymouth made a rare in-road into the opposition backline before Gareth Roberts stopped Stonebridge's shot.
Tranmere goalkeeper John Achterberg kept the scores level by turning away Paul Wotton's powerfully struck long-range shot, before Hume spurned a good chance to open the scoring after being set up by Haworth.
Tranmere came out of the traps strongly at the beginning of the second half and Haworth forced a brilliant save from Larrieu with a volley from distance.
Larrieu, though, was at fault a few minutes later when he went walkabout in his penalty area and lost the ball to Hume who crossed for Haworth to head home.
The second half was even more stop start than the first, typified by lengthy breaks for treatment to injuries on Graham Coughlan and Ryan Taylor, but Tranmere held on for a worthy win.
They were nearly undone, however in the final moments of seven minutes of injury time, when Achterberg had to be alert to thwart sub Martin Phillips, who then blasted the rebound over the crossbar.