Djokovic, the tournament's top seed in the men's bracket, defeated Mitchell Krueger in the first round 6-3, 6-2, 6-2. The Serbian had six aces in the match and only had one serve broken.
Djokovic is looking for his third consecutive Grand Slam win. He moves on to play Jo-Wilfried Tsonga in the round of 64.
Seventh-seeded Dominic Thiem beat France's Benoit Paire in five sets. Thiem took the opening two sets before Paire stormed back with 7-5, 6-1 wins. Thiem slammed the door with a 6-3 win in the fifth set.
No. 16 Milos Raonic held off Australian Nick Kyrgios in straight sets 6-4, 7-6, 6-4. It was Kyrgios' first time being eliminated in the first round in the last three majors. He made it to the fourth round in last year's Aussie Open.
In women's action, No. 1 seed Simona Halep battled with Kaia Kanepi. Kanepi won the first set 7-6, but Halep rallied from a rocky start and closed out the match with 6-4, 6-2 wins.
Fourth-seeded Naomi Osaka dominated Magda Linette, winning 6-4, 6-2 in her first match. Osaka had six aces and a 96 percent first serve win percentage.
Elina Svitolina, the No. 6 seed, also won in two sets 6-1, 6-2. She defeated Viktorija Golubic to advance to the second round. Svitolina reached the quarterfinals of last year's Australian Open.
The Williams sisters moved on to the round of 64, with Venus upsetting No. 25 seed Mihaela Buzarnescu in three sets and 16th-seeded Serena beating Tatjana Maria 6-0, 6-2.