Djokovic, who has been crowned champion in Melbourne on four occasions in total, had been the clear favourite to advance to the final four, but he found his route blocked by a sensational display from the Swiss.
ESPN's Kevin Negandhi summed up the size of Wawrinka's achievement:
The day started badly enough for Wawrinka, who may have thought a quick match was on the horizon after the World No. 2 opened with a service game to love. Although he managed to maintain pace with the Serb at 2-2, three consecutive errors saw Djokovic take a 4-2 break.
With the early lead on his side, Djokovic appeared at ease as he raced through his next service game, which saw his opponent hit three unforced errors to give himself little chance.
Djokovic's first set point came after Wawrinka pummelled the net, and despite missing his first chance, the Serb capitalised with the second.
Mistakes continued to threaten Wawrinka's output during the second set. He had three break points with the score at 1-1, but Djokovic's simple groundstrokes sent his opponent scuttling across court before a Wawrinka error saw the challenger's chance pass.
Fortunately for the 28-year-old, he continued to build momentum. Wawrinka set himself up another break after hitting a fantastic backhand winner down the line—something he repeated to take the advantage.
At this stage, Wawrinka finally looked relaxed and ready to do battle. An ace sealed the next game, and after Djokovic pulled one back, a couple of huge serves saw the Swiss clinch the second set 6-4.
Wawrinka hit an impressive 15 winners during the second set, while Djokovic managed just six, per the tournament's official website.
Roger Federer was among the support at Rod Laver Arena and was clearly in attendance to cheer on his countryman:
The third set brought on even more Wawrinka dominance as the underdog's backhand became a major feature of his play. Djokovic began to struggle with his opponent's serve on a more regular basis, losing some of his intensity, as Wawrinka wrapped up 79 percent of points from his first serve.
Wawrinka created two separate break chances—converting both—to establish a 2-1 advantage in the match. Suddenly the champion was one set from exiting the tournament, and the crowd added to the drama.
Djokovic opened the fourth set with his first double fault of the match after trying to hammer home his second serve. He nearly managed to break with the score at 2-1 in his favour, but a stunning backhand volley winner saw Wawrinka claw level—not for long.
The tide shifted back in Djokovic's favour when he concluded his second consecutive service game to love at 3-2. This was a sure-fire sign of the favourite finding his rhythm again, and indeed Djokovic showed his full range of talents with a remarkable turnaround to take the break at 5-3.
Increased aggressiveness improved the Serbian's game, forcing Wawrinka onto the back foot. A smart forehand down the line gave the struggling Swiss little chance, and with another massive forehand, the break was secured.
Three aces saw Djokovic serve out the fourth set, levelling proceedings at 2-2 overall.
A battle of breaks ensued in the fifth, with Djokovic the first to draw blood after a pinpoint forehand across court. Wawrinka immediately regained the break after a couple of errors from his opponent, and he then managed to recover two consecutive service games after conceding a break point in each.
Wawrinka led 40-15 on serve when a rain delay hit with the score at 5-5, adding a huge amount of tension to a finely balanced encounter. He served an ace after the four-minute delay, but Djokovic made it 6-6 with another love service game.
The defending champion once again began to fade from here, and it was Wawrinka who took the initiative to score a huge win. After holding another service game with confidence, Wawrinka was then aided by two Djokovic mistakes as he completed victory after fighting back from 30-0 down.
Wawrinka hit 51 winners, 17 aces and 60 unforced errors during the clash, recorded by the Australian Open's official website. Djokovic also made 60 mistakes, but he only managed 45 winners and seven aces.
Understandably, Wawrinka was extremely pleased to have finally beaten the man who has tormented him in recent times:
Wawrinka now has an exciting semifinal clash with Berdych to prepare for, an opponent he beat as recently as Nov. 4 at the ATP Tour finals, per BBC Sport.
Berdych was unable to deal with Wawrinka's serve during their recent encounter, but Djokovic's conqueror knows he will need to ensure his backhand is on form if he is to halt the upcoming Czech challenger:
Wawrinka certainly has momentum after eliminating the champion, but Berdych's ability to dictate play in his last match against David Ferrer signals this could also be a five-set battle to the end.
While Wawrinka will undoubtedly enjoy his momentous performance against Djokovic, the Swiss star will need to recover quickly if he is to enter the Melbourne final.