Ten-man Plymouth suffered their first defeat in four games as John McCombe scored twice in York's comfortable win at Home Park.
Plymouth had defender Neal Trotman sent off for a professional foul on Ryan Bowman in the box after 11 minutes.
Wes Fletcher scored from the spot with McCombe doubling the lead on half-time, heading home Bowman's cross.
York added two more after the break when McCombe poked in from a corner before Josh Carson made it 4-0 late on.
VIEW FROM THE CHANGING ROOM
York City boss Nigel Worthington told BBC Radio York:
"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.
"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 opposition's 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."
Plymouth Argyle 01 Cole 04 Blanchard 25 Purrington 11 Blizzard 16 Trotman Dismissed 17 Nelson 20 Banton (Thomas - 55' Booked ) 06 Hourihane 09 Reid Booked 08 Boco (Berry - 54' ) 07 Alessandra Substitutes 02 Berry 10 Morgan 14 Young 18 Harvey 19 Thomas 27 Gurrieri 32 Dawson York City 31 Pope 02 Oyebanjo 03 Davies 10 Penn Booked (Montrose - 79' ) 15 Lowe Booked 16 McCombe Booked 12 Carson Booked 37 Reed 09 Fletcher (Coulson - 67' ) 19 Bowman (Dickinson - 91' ) 26 Hayhurst Substitutes 05 McGurk 07 Coulson 14 Montrose 18 Platt 24 Ingham 25 Dickinson 28 Puri
Ref: Charles Breakspear