Pools were dealt a late blow at The Vic as Guiseley grabbed an injury-time winner to take the three points.
Matthew Bates's side had plenty of possession in the game, particularly in the first half, but could not find a goal to break the deadlock and after a tight second half, the visitors grabbed a late winner to snatch the points and bring Pools' unbeaten run to an end.
Bates’s side knocked the ball about well and had the greater share of possession in the first half, leaving the visitors to rely on the break for their chances on goal.
And it was Guiseley who had the first shot of the game as Alex Purver fired a shot in from the edge of the box which went wide of the Scott Loach’s post.
Josh Hawkes had the first chance for Pools on 18 minutes as he sent one wide of the near post from 25 yards out.
Dayle Southwell was next to try his luck on goal, again with an effort from distance but again his sht went wide of Loach’s goal.
Louis Laing, who played some great pinpoint crosses out of defence in the first half, went closest to opening the scoring for Pools ten minutes before the break. A corner in from Blair Adams on the right picked out the defender at the far post but his headed effort scraped the post as it went just wide.
Scott Loach had his first save to make just before the break as Purver got on the end of some decent play from the visitors to fire in a low drive on goal. Loach held the shot comfortably and the teams went in 0-0 at half time.
Guiseley had a chance early after the re-start as Southwell got through with only Loach to beat. The forward hit his effort straight at the Pools’ keeper though and then Carl Magnay arrived to clear the danger.
The visitors, who had finished the first half with a flourish, started the second half brightly and put more pressure on Pools in the opening minutes.
Devante Rodney showed his pace a couple of time to open things up for Pools at the other end but the striker lost out the first time to Harry Flowers after powering his way through into the box and fired over with his next attempt.
Sub Callum McFadzean took advantage of a slip by Lewis Hawkins to break forward and square the ball in for Southwell who was in a great position to shoot but the Guiseley man sent his effort just wide of the far post when a goal looked likely.
Josh Hawkes almost had another goal in unusual circumstances as he saw Joseph Green spill his cross at the near post but the visiting keeper eventually managed to clear.
The second half was tighter than the first as Pools had more work to do at the back than they had in the first 45 minutes.
Rhys Oates, on in place of Devante Rodney, fired a shot in from distance on 70 minutes but the shot was easily blocked by Green.
With 15 minutes remaining, Pools found themselves under pressure at the back as Guiseley upped their intensity for a spell but Scott Loach and his back four looked composed and dealt with any danger.
Oates burst down the right before squaring the ball into the middle but the ball arrived just ahead of Michael Woods who slid in to try and force it past Green.
McFadzean got in to similar effect at the other end as his ball across the face of goal went untested as the action switched from one end to the other.
Sub Ryan Donaldson sent a teasing cross in from the right late in the game which was flicked on by Oates towards goal but there was noone there to take advantage and the chance went by.
But with the teams looking set to share the spoils, a slip by Louis Laing at the back allowed Dayle Southwell through into the box and he made no mistake as he slipped the ball past Loach and into the far corner to snatch a late winner deep into injury time.
Full Time: Pools 0 Guiseley 1
Attendance: 2674 (64 Guiseley)
Pools: Loach, Hawkins, Laing, Magnay, Adams, Featherstone, Newton, Woods, Hawkes (Donaldson 79), Cassidy, Rodney (Oates 63).
Subs Not Used: Catterick, Owen, Munns.
Guiseley: Green, Palmer, Hatfield, Southwell, Purver, Odejayi (Liburd 70), Hudson (Hurst 45), Holden, Roberts (McFadzean 56), Flowers, Nirennold.
Subs Not Used: Williams, Paley.