Switzerland's Roger Federer will take on Uzbekistan's Denis Istomin, ranked 99, in what will be their seventh encounter. The Swiss have beaten Istomin on all six previous occasions.
After Disengage from his Australian Open quarter-final match with Marin Cilic last year, Rafael Nadal will kick off his season this year in Melbourne against local James Duckworth. This will be the first time the players will face each other.
The draw plant out an easy lane for Nadal in the first two rounds. A Grand Slam in the first round would set him against the winner of the match between another local, Matthew Ebden and Germany's Jan-Lennard Struff.
In the quarter-finals, he could meet Australia's Alex De Minaur, Argentina's Diego Schwartzman and the United Kingdom's Kyle Edmund.
Later, he could face Federer, against whom he lost the tournament's final in 2017, or Croatia's Marin Cilic, who will play Australia's Bernard Tomic in the first round.
Serbia's Novak Djokovic will begin his bid for a seventh title against a qualifier and could go on to meet Canada's Denis Shapovalov in the third round, Russia's Daniil Medvedev in the round of 16 and Japan's Kei Nishikori in the quarter-finals.
Argentina's Diego Schwartzman will play his first match of the Open against a qualifier and could have a third-round clash against UK's Edmund.
Fifth-ranked Juan Martin Del Potro of Argentina will miss the Australian Open due to a kneecap injury he sustained at the Shanghai Masters in October.