Wildcard Guccione had beaten second seed Richard Gasquet and Arnaud Clement en route to his first ATP final but Djokovic proved a bridge too far.
Although the players are separated by 137 places in the world standings, the 153rd-ranked Guccione produced an entertaining display to the delight of the boisterous home fans.
After almost 2-½ hours of enthralling action, Djokovic sunk to his knees and kissed the court when he secured victory following a Guccione error.
"I cannot describe the feeling I have right now," Djokovic told the crowd after donning a red Serbian soccer strip.
"We played a great match and this week has been great preparation for the Australian Open and I expect to be 100 percent ready for the Open."
Despite the loss, Guccione's heroics this week would have given Australia a glimmer of hope before the season's first grand slam gets underway on Jan. 15.
With Mark Philippoussis ruled out due to a knee injury and a question mark hanging over Lleyton Hewitt's participation after he picked up a calf strain, fans will be hoping Guccione can reproduce his form at Melbourne Park.
The lofty 21-year-old began the match by unleashing three aces and had four chances to break Djokovic in the next game, which lasted 12 minutes.
Guccione's mistimed returns allowed Djokovic to hang on and he capitalised by breaking the Australian twice to clinch the first set.
With neither player gaining a breakthrough in the second set, the match headed into a tiebreak.
Djokovic was left fuming at the umpire when Guccione nosed 7-6 ahead, believing the ball had dipped beyond the baseline.
The Serbian was jeered by the crowd as his anger spilled over and Guccione bagged the set on the next point with a fizzing crosscourt volley.
The top seed did not let his anger distract him and galloped to a 2-0 lead in the third set before extending it to 4-1.
Guccione, however, refused to bow out tamely.
Despite not having held a break point since the second game of the contest, he produced a series of sizzling winners to gain his first break to close the gap at 4-2 in the decider.
The Australian came within a whisker of leveling the match but a determined Djokovic would not be denied and grabbed his third title in less than a year