The Lions made a decent start to the game as Ash Palmer went close when his header was saved and then Michael Rankine saw an effort cleared off the line.
Palmer though soon had to come off and left via a stretcher and was replaced by Marcus Williams.
The Lions keeper Jonny Maxted was being kept busy and he was unable to keep out an effort from Jordan Nicholson who had been given room to shoot.
Guiseley made a good start to the second half when Rankine found the net, but things would quickly go downhill for the visitors.
First, Reece Styche was brought down in the area for a penalty, it was taken by Joe Ironside and Maxted saved, but just a minute later he scored to give them the lead and from that points onwards, things went from bad to worse for Guiseley.
It was then the turn of Nicholson to score a quick fire double that ended the game as a contest, he then added another to his total with a calm finish.
Lockwood’s side were now playing for pride and gained a penalty but Simon Walton’s effort was saved, in what was becoming a miserable day.
Nicholson got his fifth, taking advantage of a failed clearance and he would leave the pitch to a round of applause and rightly so as his efforts helped Nuneaton beat the team who are a league above them.
Speaking after the game, Guiseley boss Adam Lockwood said: “Nuneaton were exceptional, they were good. Our individual performances were some of the worst I’ve seen in a long time.
“I would like to apologise to the fans. This was well under-par for this club, it will be talked about and addressed.”
Meanwhile, in National North Nine man Harrogate Town defeated Bradford Park Avenue 1-0 at The CNG Stadium.
Simon Ainge headed Simon Weaver’s side into the lead after ten minutes, but the game changed on the stroke of half-time as JP Pittman was shown a straight red card.
Town’s captain and goal scorer Ainge was then also given his marching orders after picking up a second booking in the 64th minute.
It looked as though Avenue would level when they were awarded a spot kick in the 69th minute only for Peter Crook to pull off a fantastic double save to deny Nicky Boshell and hand Town all three points.
Elsewhere, FC Halifax Town got their promotion push well and truly back on track as they thrashed Tamworth 6-2. Three goals in five minutes from Richard Peniket, Matty Kosylo and Adam Morgan put Town in control, with Peniket, who was later sent-off, adding a fourth just before half-time.
Substitute Aaron Opoku got one back for Tamworth, but that proved a false dawn as Morgan added a fifth after Peniket’s dismissal before Kosylo racked up the half-dozen.
OSSETT Town slipped down to third place in the First Division North after conceding a last-minute goal in a 2-1 home defeat to Colne.
Oliver Wood gave the visitors the lead before the break but an own goal from Nosakhare Aghayere brought Town back level.
However Mark Ayres’ late strike won all three points for Colne.
Sixth-placed Farsley Celtic missed the chance to make up ground when their home game with Clitheroe was postponed due to a frozen pitch at Throstle Nest.
Ninth-placed Brighouse Town suffered a disappointing 2-1 defeat at Burscough on Saturday.
Callum Mahoney gave the hosts a sixth-minute lead only for Town to equalise through Thomas Dugdale five minutes later.
But Elliott Nevitt’s 90-minute goal proved to be the winner for Burscough.
Tadcaster Albion put in a spirited and gutsy performance to earn a 0-0 draw Colwyn Bay – playing with 10 men for over 75 minutes after the dismissal of Jono Greening.
Fourth-from-bottom Ossett Albion came away with nothing from their trip to struggling rivals Prescott Cables, going down 5-0.
Prescott’s goals came from Christopher Almond (2), Dominic Marie (2) and Dominic Reid.
Fifth-placed Scarborough Athletic slipped to a 3-1 home defeat against the leaders Lancaster City.
A BRACE from Joe Walton helped Liversedge chalk up an impressive 5-2 victory at Armthorpe Welfare in the Premier Division on Saturday.
Rhys Davies gave Liversedge the lead on four minutes but two goals from Liam Radford – the second from the penalty spot – saw the home side take the lead.
It didn’t take Liversedge long to respond. Walton brought the visitors level within a minute of the spot kick and Vaughan Redford made it 3-2 on 51 minutes.
Walton’s second goal on 73 minutes and a 90th-minute own-goal from Adam Storrie saw Liversedge canter to victory.
Mid-table Garforth Town enjoyed a 3-0 victory over Hemsworth Miners Welfare in a hard-fought Yorkshire derby.
Mark Simpson opened the scoring for Garforth on 50 minutes before a late brace from Jack McMurrough sealed the three points.
Elsewhere in the Premier Division, Stephen Bromley’s 39th-minute goal was enough to earn Harrogate Railway Athletic a 1-0 victory at AFC Mansfield.
Second-placed Pickering Town’s game against Worksop Town was postponed due to a frozen pitch.
Division One leaders AFC Emley’s winning run came to end when they defeated 3-1 at Teversal.
Two goals from Craig Mitchell and a James McCann effort put the hosts 3-0 up before Ashley Flynn netted Emley’s consolation goal six minutes from time.
Pontefract Collieries moved up to fourth place with a remarkable 9-0 trouncing of Ollerton Town in which Christopher Jackson netted five times in 21 minutes.
Pontefract’s other goals came from Spencer Clarke, Luke Jeffs, Jordan Turner (2).
Yorkshire Amateur had to settle for a 3-3 draw with Shirebrook Town despite having led 3-1 with half an hour to play.
Amateur’s goals came from Adam Shaw and two from Joel Hughes.
Elsewhere, Glasshoughton Welfare went down 2-0 at Rossington Main while second-placed Penistone Church kept up the pressure on AFC EMley with a 4-0 victory over basement side Nostell Miners Welfare.