Nigel Worthington got the better of his former Sheffield Wednesday team-mate John Sheridan as York City moved up the League Two table.
The Minstermen are now up to 11th in the table after goals from Wes Fletcher, John McCombe (2) and Josh Carson punished 10-man Argyle.
Plymouth defender Neal Trotman was sent off for a professional foul on Ryan Bowman after just 11 minutes.
Fletcher scored from the resulting penalty before McCombe headed home Bowman’s cross.
McCombe doubled his tally from a corner before Carson banged in a late strike.
“Plymouth’s always a very tough place to come and whether it’s for or against you, you never like to see a player getting sent off,” said York boss Worthington, a former team-mate of Plymouth boss Sheridan at Hillsborough in the Nineties.
“I’ve been in that situation many times before when I’ve either been down to 10 with my own team as a player or manager or the oppositions been down and they can make it very difficult.
“Plymouth kept their shape and kept working hard but the one thing we had to do at half time was make sure we stayed professional and keeping doing things simple.
“Great credit to the players, we did that.”