Jordan Preston gave the Lions a fine start when he converted Connor Brown's cross from the right flank on 13 minutes.
The hosts then found themselves two ahead when Will Hatfield's cross deflected kindly into Jake Cassidy's path and he had the simplest of tasks to nod the ball home.
The early damage could have got even better for Adam Lockwood's men on 25 minutes when Hatfield was brought down in the box, only for Cassidy to see his penalty saved.
Guiseley were then untroubled in the second period as they held onto only their fourth win of the season – moving above Woking and North Ferriby into 22nd place.
Gary Mills' wait for a first win at York City continued as Simon Heslop rescued a point at mid-table Eastleigh.
Mikael Mandron put the Southern hosts in front on 52 minutes before Heslop levelled matters with 14 minutes remaining.
In National League North, Harrogate Town went down to fourth league defeat in five games in a seven-goal thriller against play-off rivals Tamworth at the CNG Stadium.
Having twice fought back on to level terms in the first half, Warren Burrell looked to have given Town the three points in the second period.
However, Lewis Newton scored twice in the final five minutes to turn the tables again and send Tamworth home with the points.
Chib Chilaka and Simon Ainge were the two players on the scoresheet for Harrogate in the first half.
FC Halifax Town remain fourth after a comfortable two-goal win over ten-man Kidderminster Harriers.
After a goalless first half, Liam King saw a penalty saved but his blushes were saved as Matt Kosylo put Halifax ahead on 50 minutes.
A one-goal lead was held until added time when Richard Peniket made the points safe.
Elsewhere, Bradford Park Avenue gained successive wins for the first time this season after beating Alfreton 1-0 at home.
Nicky Wroe scored the only goal after 20 minutes after Nicky Boshell's free-kick had rattled the crossbar.