Top seed and six-times champion Djokovic will meet Frenchman Lucas Pouille, a maiden Grand Slam semi-finalist, on Friday for a place in Sunday's final.
Second seed Rafa Nadal and Greek wunderkind Stefanos Tsitsipas will meet in the other semi-final on Thursday.
Djokovic, bidding for a record seventh title in Melbourne, failed to reach the last four in the past two editions of the tournament as he battled with an elbow problem.
But he has roared back to his best, and is a huge favourite to win a third successive Grand Slam title after triumphing at Wimbledon and the U.S. Open.
"This has been my most successful Grand Slam throughout my career, the first one that I won back in 2008. As I said on the court, I have a lot of beautiful memories from Rod Laver Arena," he told reporters.
"Yeah, the past two years have been a bit tough with the elbow injury and everything."
Nishikori grinded through three five-set matches before taking on the Serb and was clearly struggling after a handful of games in the evening match at Rod Laver Arena.
He had a medical time-out after losing the first set and grimaced as a trainer worked on his right thigh. He pulled out of the match after Djokovic won the fifth game.
"Before the match, I was okay. Of course, I wasn't, like, fresh, fresh," the Japanese number one said.
"After the third game or fourth game when I was serving, I felt pretty heavy to my right leg. After that I couldn't really bend my knees and couldn't jump up."
Djokovic was grateful for the short match, having complained of a sore back and a "couple of issues" after battling through a taxing four-set clash against Russian Daniil Medvedev in the previous round.
"As they say this is exactly what the doctor ordered," he said in his on-court interview.
"I've had plenty of matches so far this year... And I'll do everything to get ready for that (next) one."
Djokovic has never played 28th seed Pouille, who has enjoyed a brilliant run at Melbourne Park, but has practised with him plenty of times.
The enigmatic 24-year-old had never won a match at the year's first Grand Slam prior to this year but eased past Milos Raonic in four sets.
"He struggled a little bit with consistency of his results in the last two years," said Djokovic.
"But with the quality of the tennis that he possesses, he deserves to be definitely at the top 15, maybe top 10 of the world.
"Hopefully we can both be fresh and fit and put on the great show."
(Editing by Amlan Chakraborty and Christian Radnedge)
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