Kayode Odejayi, who knows a thing or two about scoring in the competition, saw his header prove to be the match winner.
Guiseley joint-manager Russ O’Neill said: “We are over the moon to be through, the main aim is to get through and we did that.
“I have to say Cleethorpes deserve a lot of credit, it was a game where we had to get the basics right and we did that.”
Cleethorpes had two key chances early on, first a corner found Oli Donald on the edge of the area, his effort had beaten Guiseley keeper Joe Green but Kingsley James was in the right place to clear off the line.
Brody Robertson from the next attack was put through on goal, as a ball over the top split the hosts defence open, on the angle the forward saw his effort hit the crossbar.
The hosts needed to take control and had a good chance when Niall Heaton had a shot from 20 yards out, a slight deflection made it an impressive save from Dylan Parkin.
After going in goalless at the break, Guiseley started better in the second-half, with a powerful drive by Will Hatfield being well saved by Parkin.
The Lions would take the lead when Scott Smith was brought down in the area, Hatfield saw his penalty saved, but he was on hand to tap-in the rebound.
Just like Saturday, Guiseley couldn’t hold onto the lead and Jon Oglesby equalised with a fine curling effort from just outside the area, that was placed into the bottom right hand corner of the goal.
A real moment of quality would see Guiseley win this match, as Curtis Morrison delivered a pin-point Cross onto the head of Kayode Odejayi, he placed his header past Parkin and in.
As Cleethorpes tried to get back into this match, Oli Donald went into a 50/50 challenge but caught Alex Purver, he picked up a second yellow card and the visitors ended the game down to ten men.
The full-time whistle saw Guiseley pick up £15,000 in prize money and a home tie against Stourbridge in the FA Cup fourth qualifying round.
Guiseley starting 11: Green, Moyo, Thornton, Heaton, James (Morrison 45) Halls, Purver, Smith (Walters 86) Hatfield, Harvey, Odejayi
Unused substitutes: Worsnop, Clayton, Young, Hussain, Felix
Cleethorpes Town starting 11: Parkin, Topliss, Walker (North 70) Richardson (Disley 45) Lowe, Donald, Collins, Flett, Vernon (Batty 83) Robertson, Oglesby
Unused substitutes: Bloomer, McKay, Gray, Birch
Referee: Andrew Kitchen