Town headed into the break 3-2 down after Hallam Hope and Anthony Grant got on the scoreboard for the Reds. Conor Grant's late free-kick put the game out of sight meaning the three points were staying in Devon.
Town fell behind inside six minutes with Luke Jephcott beating goalkeeper Matej Kovar to the ball and heading into an empty net.
The Pilgrims doubled their lead within minutes of the restart when skipper Joe Edwards got on the end of a Ryan Hardie cross, giving Town a monumental hill to climb.
Three minutes later Town did get on the scoresheet when Dion Donohue made a burst into the box and cutting back to Hallam Hope who slotted into the bottom left-hand corner.
Just before the twenty-five minute mark Town were level. Jack Payne’s in-swinging corner found the head of Anthony Grant who diverted towards goal and Panutche Camara’s stray leg stuck the ball past his own keeper.
Almost immediately Plymouth regained the lead via Jephcott, who tapped into an empty net after a Hardie cross.
Moments before the half-time whistle, referee John Busby turned to Jonny Smith, who was already on a yellow card, and showed him a second caution for what could have only been dissent and gave the winger his marching orders.
The second forty-five was much more disciplined from Town, only conceding a late free-kick from Conor Grant.
Plymouth had the first real chance of the half when Panutche Camara rattled the post on the edge of the area, but the rebound bounced blackout and away from danger.
Town had a good chance to draw things level when Anthony Grant’s lofted pass over the Plymouth defence found substitute Brett Pitman. The striker did well to get to the ball but it skipped off the wet surface and was collected by Cooper.
With only a few minutes to go, Conor Grant placed a free-kick into the top left-hand corner securing the points for the Pilgrims.
The boys suffer their sixth defeat in the league this season heading into an FA Cup tie with National League North side Darlington on Saturday.