The result heaped more pressure on beleaguered York boss Jackie McNamara, who has still not won an away game during his 11-month tenure.
Not even an hour-long delay for a 40th-minute floodlight failure could save the Minstermen’s blushes with the score at that stage 4-1 – the home side’s first-half efforts all netted in a 12-minute period.
Jake Cassidy, Alex Purver, Will Hatfied, Jordan Preston, Jermaine Hylton and Rob Atkinson all made the scoresheet for the hosts.
This after York had made the early running and gone ahead on 11 minutes when Matt Fry headed into the top corner from Danny Galbraith’s corner.
After play restarted and the regulation 15-minute interval was carried out despite the long delay, Guiseley continued to dominate.
Hylton deserved his 55th-minute goal when, following another Kamdjo error, he was played clear by Simon Walton and beat Letheren with a composed finish.
A far-post header from ex-York striker Adam Boyes then set up Atkinson to sweep in from 10 yards on 82 minutes and complete the rout.
Guiseley: Maxted; Brown (Clee, 72), Lawlor, Atkinson, Lowe; Hatfield, Purver, Walton, Preston; Cassidy (Rankine, 77), Hylton (Boyes, 81). Unused substitutes: Atkinson, Palmer.
York City: Letheren; Rooney, Kamdjo, Fry, Barber; Clappison (Klukowski, 46), Dixon, Heslop; Galbraith, Fenwick (Murdoch, 46) Johnson (Felix, 60). Unused substitutes: Simpson, Felix, Clarke.
Referee: David Richardson.