In a week where Micky Adams resigned from Tranmere, this game would effectively decide Tranmere’s fate in the Football League.
Plymouth took the lead after seven minutes when Max Power was judged to have brought down Dominic Blizzard.
Reuben Reid added to his ever-growing goal record as the tucked away his penalty.
Power then made up for his mistake when he hit home after thirty-four minutes to bring the scores level.
Disaster struck for Tranmere when Tareiq Holmes-Dennis hit a spectacular twenty-five yard strike to put Plymouth back in the lead after Rory Donnelly had dwelled on the ball.
Into the second half, Tranmere had a good chance to equalise when a well worked free kick was played to Jason Koumas who crossed the ball into the box only for Kayode Odajeyi to squander a header.
Plymouth then increased their lead when Lewis Alessandra tucked home.
Odajeyi then struck on eighty-nine minutes but it was too late for Tranmere.
The result means that Tranmere are relegated after ninety-four years in the Football League with Cheltenham joining them in the Conference next season.