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The Serbian world number one eased into his ninth decider at Melbourne Park with a 6-3 6-4 6-2 win under the lights at Rod Laver Arena and will battle either Stefanos Tsitsipas or Daniil Medvedev for the title.
Djokovic's tournament appeared on a knife edge when he suffered an abdominal injury during his third round match against Taylor Fritz less than a week ago.
Yet he has put that aside and will have two days off to recover before Sunday's final.
"This is the best I felt during the entire tournament," he told Jim Courier on court.
"Felt great, I could swing through the ball, no pain, just best match so far, and it came at the right time and I'm thrilled to feel this way.
"Recovery is priority right now. I'm feeling the ball well, I'm playing well, I had enough match play, enough practice so right now it's just gathering all the necessary energy for the most important match of the Australian Open."
Djokovic has never failed to win the tournament after making the semifinals and he will be heavily favoured to claim a record-extending ninth title at his favourite Slam on Sunday.
While Karatsev would have been regarded one of Djokovic's more unlikely semifinal opponents, the world number 114 put up a decent show at Rod Laver Arena as fans returned to Melbourne Park following a five-day lockdown.
He broke Djokovic twice in the match and came back from 5-1 down in the second set to briefly rattle the Serb.
Karatsev saved two set points as Djokovic served at 5-4, and swung freely to prise two break points from the champion.
Djokovic fired two huge serves to cancel the threats before sealing the set and took the momentum into the third as he broke Karatsev in the opening game.
Karatsev rallied again to level to 2-2 but a long tournament appeared to take its toll as Djokovic raced away and sealed the match with an ace.
"We need to give him a hand. Huge congratulations to him," Djokovic said of the 27-year-old Karatsev, who reached the main draw of a major for the first time after failing to qualify at nine previous Grand Slams.
"On his debut he reached semifinals, I don't think it's ever happened in the history of tennis, so well done to him. He played a great tournament."