Second seed Casper Ruud - twice a runner-up on the Grand Slam stage last year - plays Tomas Machac.
A pre-tournament practice match between Nick Kyrgios and Djokovic saw tickets sold out in 58 minutes and the pair could potentially meet in a blockbuster quarter-final.
Five-times runner-up Andy Murray plays Matteo Berrettini while fifth seed Andrey Rublev meets wildcard Dominic Thiem in other first-round matches.
The Polish player could face seventh seed Coco Gauff in the quarter-finals and third seed Jessica Pegula in the semi-finals.
Women's world number two Ons Jabeur will begin her latest attempt to become the first Arab player to claim a Grand Slam singles title when she plays Tamara Zidansek.