Chorley won thanks to goals from Josh Wilson, Adam Blakeman and Alex Newby.
Guiseley joint-manager Marcus Bignot said: “It was a tough game, we have faced a good side who in my opinion will be going up.
“If we can say we’ve learnt something from it ten that is something, we now have to focus and aim to bounce back quickly.”
The last time these sides faced in the Vanarama National League North at Victory Park, it was when Guiseley came back from 2-0 down to win and gain promotion over three years ago.
This time around, Chorley were the side looking up as they sat at top spot and knew whatever happened they would end the day there.
The hosts started brightly and took the lead with just five minutes gone, it was an ex Guiseley striker who finished a well-worked move as Josh Wilson scored from five yards out.
Chorley impressed throughout, with Alex Newby seeing an effort from 25 yards out go just wide.
There would be one key chance for Guiseley before the break, as the Lions broke with Curtis Morrison crossing for Kayode Odejayi who just couldn’t make contact from a few yards out.
Chorley kept going with impressive passing and Marcus Carver was this time denied by Dewhurst who got a strong hand to the drive and got it out of play.
The start of the second-half, saw Chorley double their lead immediately, Andy Teague from centre-back found Adam Blakeman on the left wing he worked his way into the Guiseley half and from 25 yard out hit a clean strike that flew into the bottom right-hand corner.
The game was gone for Guiseley and the hosts were now starting to really impress, some fine passing led to their third, a move that involved eight passes led to Alex Newby having a shot on the edge of the area that left Dewhurst with no chance.
Chorley really should have added to their tally but in the end it ended 3-0.
Elsewhere, Bradford Park Avenue were held 1-1 at home by Blyth Spartans.
But Steve Watson failed to win on his debut as York City manager, losing 3-1 at Stockport County.