An Alex Purver strike with 15 minutes to go proved to be the difference between the two sides.
After the disappointment of losing at the weekend at Hereford, Guiseley started brightly, a corner was swung in and found Kaine Felix who flicked the effort past Curzon keeper Cam Mason but two defenders on the line were able to clear it away.
The hosts had an even better chance to take the lead soon after, another corner found Scott Garner who powered his header against the bar and it was eventually cleared.
Momentum was being built by the hosts but they suffered a blow when Lewis Archer on his home debut went off with a knock that seemed to affect the players.
Curzon had their first real opportunity just before the break, when Luke Wall ran into the area, on the edge of the box he aimed towards goal but Purver did well to get his body in the way.
Wall had an even better chance when he shot from the edge of the area, it looked to be going in but Andy Halls got a vital touch on the ball and it went narrowly wide.
Guiseley would finally score a goal for the first time in five and a half weeks in the league when a long throw wasn’t cleared, it fell to Purver who showed real persistence to place his effort into the bottom left-hand corner.
There was tension in the air during the closing stages but the Lions saw the game out and left with a big three points.
Guiseley joint-manager, Russ Wilcox, said: “It is a big three points, to get the goal, the clean sheet, it was a great evening for us all.
“We now have that home win and want to build on it against York at the weekend.”
Guiseley: Dewhurst, Cantrill, Garner, Halls, Langley, Purver, James, Felix (Morrison 66), Barkers, Archer (Odejayi 40), Dyche (Moyo 90).
Unused substitutes: Clayton, Digie
Curzon Ashton: Mason, Thornley, Senior McJannet, Hunt, Rowney (McAtee 80), Crankshaw, Brooke, Reilly (Deakin 85), Miller, Wall (Wardle 80).
Unused substitutes: Shenton, Shaw
Referee: Michael Barlow