Despite some determined motocross style efforts to get back into the race – causing him to drop the bike again at one stage -, Rea would eventually concede defeat and retire into the pit lane.
Once again throwing the title race wide open, Sykes was promoted back into the lead with nine laps remaining, but it was clear he didn't have the pace to sustain his position for much longer as the threat of Melandri and Guintoli loomed.
Having broken away from a busy chasing pack, Melandri and Guintoli were embroiled in their own private fight as they quickly made gains on Sykes.
An impressive effort by Melandri considering his back injury, the BMW rider looked on course to overtake Sykes when he cruised onto his tail, only to be caught napping on the exit of turn 17 to allow Guintoli to jump ahead, much to the delight of the home crowd.
Taking just two more corners to nose ahead of Sykes, though Melandri would quickly follow suit, Guintoli was already away into the lead.
Buoyed on by the home support, Guintoli extended his margin over the remaining six laps to cross the line as a winner for the third time this season, yet again in tricky weather conditions. His second triumph with PATA Ducati, having also won a race with former employers Effenbert Liberty, Guintoli's victory signals a fitting final round success for the outgoing Ducati 1098R and PATA, who will revert from team owner to Honda's title sponsor in 2013.
Melandri held on for second place, in doing so improving chances of winning the title. Though he remains a fair 18.5 points off Biaggi, at worst he is also just four points behind Sykes for the runners-up spot.
Sykes, meanwhile, kept it neat and tidy for third position, but will still need yet more luck in the final race of the season if he is to overhaul Biaggi.
Already a depleted grid of just 19 riders following pre-race injuries for John Hopkins and Alexander Lundh, the race suffered high attrition with just ten riders reaching the chequered flag on the lead lap.
As such, there were some notable results off the podium with Maxime Berger providing more joy for the home crowd as he broke through for fourth place, his – and the team's - best-ever WSBK result coming on his first outing with the Red Devils Roma Ducati team.