AFP Sport takes a look back at his breakthrough triumphs at all four Slams:
2008 Australian Open
Then just 20, Djokovic arrived in Melbourne on the back of a runner-up finish at the 2007 US Open to Roger Federer, the first of the Serb's 34 Grand Slams finals.
Djokovic swept through the early rounds untroubled, easily dispatching home favourite Lleyton Hewitt along the way, before sweeping aside David Ferrer to set up a rematch with Federer for a place in the final.
Federer, the world number one, was the two-time defending champion but Djokovic took the Swiss down in straight sets to end his rival's record streak of 10 consecutive major finals.
It was also the first Slam final without Federer or Rafael Nadal in three years, the Spaniard thrashed by unseeded Frenchman Jo-Wilfried Tsonga in the last four. Tsonga had shocked Andy Murray in round one.
Tsonga won the opening set of the final but Djokovic fought back to claim the title, emerging 4-6, 6-4, 6-3, 7-6 (7/2) to secure the first of a record 10 Australian Open crowns.
2011 Wimbledon
Having ended a three-year wait for his second major in Australia, Djokovic would embark on an astonishing 41-match unbeaten run in 2011 -- one of the greatest seasons in the sport's history.
His streak ended in defeat to Federer in the Roland Garros semi-finals, but Djokovic returned to action at Wimbledon three weeks later hungry for more success.
Seeded second to Nadal, Djokovic dropped one set en route to the quarter-finals where he met the unpredictable Australian Bernard Tomic.
Djokovic advanced in four sets and in the next round saw off a battling Tsonga, who had stunned Federer from two sets down in the last eight.
That set up a rematch of the 2010 US Open final won by Nadal. This time, Djokovic got the better of the Spaniard, powering through the first two sets before completing a 6-4, 6-1, 1-6, 6-3 victory.
2011 US Open
Djokovic touched down in New York with questions over the health of his shoulder after he retired against Murray in the final of the tune-up event in Cincinnati.
He quickly dispelled any concerns by dropping just three games in the first two rounds, cruising through to the quarter-finals before compatriot Janko Tipsarevic called it quits in the fourth set.
Djokovic's next match was one of the defining moments of his career. After hauling himself back from two sets behind against Federer, Djokovic was down double match point at 3-5 with the Swiss serving.
The Serb uncorked a sensational return, admitting later the shot was a gamble, but it was one that sparked an improbable comeback as Djokovic reeled off the final four games to stun his incredulous rival.
Twelve months on, Nadal again stood between Djokovic and an elusive US Open title. It was very much Djokovic's year though -- going 10-1 against Nadal and Federer -- as he downed the Spaniard 6–2, 6–4, 6–7 (3/7), 6–1 to capture his fourth Slam.
2016 French Open
Nadal's near-total stranglehold on the Coupe des Mousquetaires frustrated Djokovic, twice beaten by him in the French Open final, in 2012 and 2014.
Even when Djokovic finally defeated Nadal at the seventh attempt in Paris in the 2015 quarter-finals, he fell to Stan Wawrinka in the final.
But the following year, with Nadal pulling out in the third round due to a wrist injury and Federer skipping the tournament to preserve his health, Djokovic sensed it was his moment at long last.
He conceded a single set in getting to the final, crushing Tomas Berdych and Dominic Thiem to set up a showdown with Andy Murray -- the man he beat five months earlier to win the Australian Open.
Murray pocketed the first set, but Djokovic roared back emphatically to prevail 3–6, 6–1, 6–2, 6–4 and complete a career Grand Slam. He also became the first man since Rod Laver in 1969 to hold all four Slam titles at the same time.
