Djokovic, who is playing after a six-month injury lay off, defeated Spaniard Albert Ramos-Vinolas in straight sets 6-2, 6-3, 6-3.
The six-time Australian Open winner received a medical treatment in the second set for an injury but came back strong to close out the match in two hours, 23 minutes.
Djokovic will next face South Korean Hyeon Chung in the round of 16.
Meanwhile, Maria Sharapova's hopes of a title-winning return to the Australian Open were crushed by Angelique Kerber 1-6, 3-6. (ANI)