The Pilgrims led through Gavin Allott, only to be pegged back by Kayode Odejayi and Rowan Liburd before a Jay Rollins brace handed United a 3-2 half-time lead.
Brad Abbott and Lewis Gibbens were on target after the break in between two more Liburd efforts as the Pilgrims held on for a memorable three-point haul at Nethermoor Park.
With the Pilgrims naming an unchanged XI, new signing Nicky Wroe had to be content with a place on the bench.
The visitors took a 15th minute lead when ALLOTT tucked home the rebound after Andi Thanoj’s long-range drive had deflected onto Marcus Dewhurst’s crossbar.
The lead lasted just three minutes though and Liburd sprayed the ball into the path of marauding full-back Cliff Moyo and his deep cross to the back post was powered home by the head of ODEJAYI.
LIBURD turned from provider to scorer when he put Guiseley in front two minutes further on with a fine drive into the corner from 20 yards.
United responded less than 120 seconds later with Ashley Jackson sliding ROLLINS into the clear and he stabbed an angled finish past Dewhurst, despite Andrew Halls’ close attentions.
Boston re-asserted their lead in the 28th minute when ROLLINS, making his 100th start for the club, smashed the ball home after Gibbens had kept alive Davies’ deep cross from the right.
There was a reprieve for United at the end of the half with George Willis saving well to deny Liburd and Alex Purver rattling the post with the follow-up.
LIBURD did restore parity two minutes after the break when he arrived at the back post to steer home Purver’s cross-shot from the right.
Wroe was introduced for his debut in the 69th minute and the Pilgrims were back in front two minutes later when ABBOTT crashed home the loose ball after Nicky Walker’s cross had landed kindly for him.
United added a decisive fifth five minutes later when GIBBENS arrived at the back post to head home Davies’ deep cross from the right.
There was still time in stoppage time for LIBURD to complete his hat-trick with a back post header and Rollins motor clear before spurning his own treble chance — but the Pilgrims held on.
Guiseley (4-4-2): Marcus Dewhurst; Cliff Moyo, Andrew Halls, Will Thornton (Paul Clayton 82), Niall Heaton; Scott Smith (Curtis Morrison 79), Alex Purver, Will Hatfield, George Cantrill; Rowan Liburd, Kayode Odejayi. Subs (not used): Aleks Starcenko, Kingsley James, Jon Worsnop (gk).
Boston (4-4-2): George Willis; Ben Davies, Ryan Qualter, Lewis Gibbens, Ashley Jackson; Max Wright (Nicky Walker 56), Brad Abbott (Spencer Harris 86), Andi Thanoj, Jonathan Wafula; Gavin Allott (Nicky Wroe 69), Jay Rollins. Subs (not used): Callum Chettle, Andre Johnson.
Referee: Nathanael Cox.