This defeat was also compounded by a red card for Jamie Spencer who picked up two yellow cards, in what was a day to forget for the side who started the game on top of the table.
The Port made the ideal start, taking the lead after just 50 seconds, a Raul Correia pass found Jack Sampson and he had a simple finish as he kept his impressive record of scoring against the Lions making it three in his last three games against the side.
Ex-Guiseley loanee Correia would double the home side’s advantage after a cross found him just a few yards out and he simply could not miss with a tap-in.
Just moments later Guiseley would have their best chance of the match, as Kaine Felix on a narrow angle, hit a powerful effort towards goal but Southport goalkeeper Dan Hanford did well to tip the effort away at full stretch.
The wind was certainly having an impact on this match, and there were few chances for the rest of the half and the game in general.
A good start was essential for Guiseley in the second half, but again they conceded early instead, the impressive Kieran Glynn was able to cut inside and placed his shot into the bottom right-hand corner.
The game was effectively over as a contest and Guiseley’s day made worse when Spencer picked up another booking with just over 20 minutes to go.
After the defeat Guiseley joint-manager Marcus Bignot said: “It is obviously disappointing to lose the unbeaten start. The early goal had an impact and we just have to pick ourselves up and look ahead to the next match.”
The Lions now look to get back to winning ways tomorrow when they host Spennymoor Town.
Meanwhile, Farsley Celtic fell to a first defeat of the season following a hard-fought 2-1 loss to promotion favourites Chester.
Second-half strikes from Bradley Jackson and George Waring were enough for the hosts to secure all three points despite Will Hayhurst’s penalty for the Celt Army.
After a quiet opening to the game Elliot Wynne was forced into action for the first time 20 minutes in, saving well at his near post from Joel Taylor’s powerful strike.
It took Chester less than a minute after the restart to take the lead, the ball dropping to Jackson in the right corner of the penalty area, with Jackson firing a superb strike past Wynne.
The Blues doubled their lead just after the hour mark, Jackson this time turning provider as he picked out a wide-open Waring who coolly slotted home at the back post.
After a sustained period of pressure the Celt Army pulled a goal back, Hayhurst converting the spot-kick after Paul Walker had been tripped in the box.
Despite Farsley dominating the ball, chances for an equaliser failed to develop, and Chester hung on to secure the three points.
“I felt it was a tough game,” said a disappointed Farsley Celtic boss Adam Lakeland after the game. “It’s a difficult place to come against a tough team.
“I don’t like losing games of football so I’m disappointed today, but when the fixtures come out and you look at that first week you think ‘flippin’ heck, it’s going to be tough this’.”
“If we could try and win the home game and try and pick up something away from home at Chester and York, we probably would have taken that.”
In the National League, Harrogate Town slipped to a 1-0 defeat at Woking while leaders FC Halifax Town made it three wins out of three thanks to a 1-0 home victory over Dagenham and Redbridge.
Liam McAlinden netted the all-important winning goal for the Shaymen.