Ian Henderson was the home team's hero, combining with George Donnelly to release Jamie Allen for the fifth-minute opener before rifling a superb half volley.
By that time Plymouth's Andres Gurrieri had received his marching orders for an elbow on Jack O'Connell and it was left to Michael Rose to add gloss to the scoreline.
Keith Hill's men are now two points behind leaders Scunthorpe United, who were held to a goalless draw at AFC Wimbledon after capitalising on a woeful outing for fellow promotion chasers Chesterfield.
Paul Cook's men were undone by two goals in as many minutes from Southend United duo Ryan Leonard and Barr Corr, having seen Kevan Hurst open the scoring.
A 3-0 and Chesterfield's drop to fifth, a place behind their opponents, was confirmed after Marc Richards missed a penalty for the beaten visitors
Burton Albion lie third despite sharing a 0-0 draw at Bury, who sit two points above the relegation zone.
Third-bottom Bristol Rovers recorded the same scoreline at York City, while the showdown between the Football League's two lowest ranked teams, Torquay United and Northampton Town, was postponed due to a waterlogged pitch at Plainmoor.
The scheduled games between Exeter City and Morecambe and Newport County and Dagenham and Redbridge suffered a similar fate.
Accrington Stanley have a buffer of three goals between themselves and the drop zone following a first win in five matches at Cheltenham Town.
George Bowerman and Luke Joyce netted first-half goal for James Beattie's side before veteran Cheltenham striker Jamie Cureton set up a grandstand finish, though the visitors held on for a 2-1 win.
Mansfield are a point and a place better off than Stanley thanks to their 1-1 draw at Portsmouth.
Fleetwood Town and Oxford United close out the top seven and maintained their promotion ambitions with wins over Hartlepool United and Wycombe Wanderers.
Alex Marrow, who rejoined Fleetwood on loan from Blackburn Rovers this week, completed a 2-0 win after burly frontman Jon Parkin smashed home, while Nicky Wroe struck the only goal three minutes from time at Adams Park – where Wycombe's Steven Craig received a needless first-half red card for elbowing Johnny Mullins.
