In a marathon encounter that lasted one minute shy of three hours between the top seeds, Djokovic dropped a set against Musetti on a hard court for the first time as the Italian battled to win the match and seal his place at the ATP Finals in Turin.
However, Djokovic recovered to win the second set, showing no signs of his advancing years when he stretched at the net to play a cross-court drop shot, doing the splits at full stretch that got the crowd roaring its approval.
The drama reached fever pitch in the decider when an exhausted Djokovic was broken serving for the title at 5-4.
However, he rallied once again to break Musetti before finding his last reserves of energy to serve out the contest and eclipse Roger Federer by claiming a record 72nd hard court title.
Djokovic was initially too exhausted to celebrate, but after embracing the 23-year-old Musetti, the Serbian ripped his own t-shirt as he roared in delight.
'Gruelling match'
"Incredible battle. It's just, I don't know, three hours... a gruelling match physically, super demanding. Lorenzo played really well," Djokovic said while catching his breath.
"It could have been anybody's game, anybody's match. So congrats to him for an amazing performance, and I'm just very proud of myself to get through this one."
Djokovic is now two titles behind Federer in the ATP Tour's all-time list while Jimmy Connors leads the way with 109.
The result saw Musetti lose out on the last ATP Finals spot, allowing Canadian Felix Auger-Aliassime to qualify for the tournament in Turin.
"Novak, every time I share the court with you, I take it as a lesson," said the humbled Italian.
Djokovic now turns his attention to the ATP Finals, where he is set to play his first match on Monday. The Serbian is in the same group as Carlos Alcaraz, Taylor Fritz and Alex de Minaur.
