It was a remarkable performance from the world No 1 whose body language for the first two sets suggested he was suffering physically.
Indeed, it was not until the latter stages that Djokovic finally displayed some of the form which saw him dominate the rest and win three grand slam crowns in 2011.
Fifth seed Ferrer, as always, was a game opponent but lacked the weapons to trouble Djokovic, who ran out a 6-4 7-6 (7/4) 6-1 winner to advance to a clash with Andy Murray in a repeat of last year's final he won comfortably.
When quizzed about a possible fitness issue afterwards, Djokovic was giving nothing away.
"You have to hang in there, David is a great competitor and he always makes you hit every shot," he said. "I wasn't feeling very fresh.
"It was a great match, we played for almost three hours - I think the first 30 minutes was just for the first two games.
"I was lucky to get out of the second set and that was a big mental advantage to go two sets up."
It was a result which further emphasised the gulf between the top four players and the rest as a seemingly struggling Djokovic beat the fifth best player in the world convincingly.
Although evident at the end, there seemed little between them in the early stages as Ferrer matched Djokovic stroke for stroke in some punishing baseline exchanges.
And it took a moment of brilliance from the top seed to break for 3-2 with a stunning forehand.
Despite being pushed when serving for the set he got the job done and then broke in the opening game of the second.
He may have been in command on the scoreboard but Djokovic's demeanour was not that of a man enjoying his evening's work.
Ferrer, perhaps sensing all was not well with his opponent, broke back for 2-2 and the momentum swung further in his favour when Djokovic pulled up sharply in the next game clutching his hamstring.
The top seed battled on though and even broke for a 6-5 lead only for Ferrer to hit straight back. The tie-break would prove the pivotal moment of the match.
Ferrer led 4-2 but Djokovic showed great resolve to battle back and claim the next five points and finish the set with his first fist pump of the night.
The third set was a cruise as Djokovic finally freed his shoulders and Ferrer wilted.
Despite sometimes being caught flat-footed by the flamboyant Nishikori, Murray ended the 22 year old's historic run 6-3, 6-3, 6-1 in just 2 hours and 12 minutes.
Murray is now into his fifth consecutive grand slam semi-final as he seeks the first major win by a British man in 76 years, and is still on course for his third straight Melbourne title match.
After heavy defeats by Roger Federer and Djokovic in the past two finals, Murray has progressed almost unnoticed, but Ivan Lendl's new charge is unbeaten this year and has dropped just one set in reaching the last four.
Importantly Murray, whose previous opponent retired hurt, has been barely detained on court so far, leaving him physically fresh for his semi-final.
"I'm going to have to play a lot of long points and a lot of tough points against either Ferrer or Novak, so it's good that I'm fresh," Murray said.
Four-time winner Roger Federer and Rafael Nadal, the 2009 champion, will be in action in the other semi-final on Thursday.
In the women's draw, burgeoning star Petra Kvitova and glamorous Russian Maria Sharapova set up a hotly anticipated rematch of last year's Wimbledon decider with quarter-final wins Wednesday.
Kvitova, who enjoyed a breakthrough victory over Sharapova at Wimbledon in July, beat Italy's Sara Errani 6-4, 6-4, before Sharapova ended the fairytale run of 56th-ranked Ekaterina Makarova 6-2, 6-3 to reach the semi-finals.
It is the first time Sharapova has reached the final four in Melbourne since 2008, when she claimed the most recent of her three major trophies.
The photogenic blonde has since suffered injury problems and she said her return to contention for grand slam titles vindicated her hard work in recovery and training.
"It's been a long road back to this big stage, but after hitting the winning shot you look back and think everything was worth it, no matter how tough it was," she said.
Later on the centre court, Nishikori wowed the crowd with a between-the-legs trick shot but could not produce the tennis to seriously trouble the British number one and fourth seed Murray.
"I thought it was a good match. There were a lot of good points. Most of the fun points he was winning so I was trying to keep them as short as possible," said Murray, who was on target with only 44 percent of first serves.
"I need to serve better. I didn't serve particularly well but the returning was good so that was a positive," he added.
Murray broke the Japanese 24th seed seven times in total while he was broken twice. Murray, still seeking his first grand slam win, is unbeaten this year after he won the Brisbane title earlier this month,
Nishikori, the highest male Japanese player in rankings history, was the first Japanese man to reach the quarterfinals of the Australian Open in the open era.