The world number one, bidding to become the first man in the professional era to win three successive Australian Open titles, meets France's Paul-Henri Mathieu in the final game of the day session on Rod Laver Arena.
"There is no underestimating him, that's for sure," the Serb said of the 31-year-old right hander, who has won four titles on the ATP Tour.
"Maybe he's lower ranked at this moment but he was a top-20 player. He knows how it feels to play on a big stage."
Mathieu was ranked as high as 12th in the world five years ago but needed surgery on his left knee and missed all of 2011.
He entered 2012 as an unranked player and finished 59th in the world, advancing more than 1,500 places in the rankings and Djokovic was preparing for a battle.
"You just try to take one match at a time, focus on your next opponent, your next challenge," the 25-year-old added.
"I'm going to try to focus from the start."
Local fans will also have plenty to look forward to on the tournament's opening day with sentimental favourite Lleyton Hewitt due to take on eighth-seeded Serb Janko Tipsarevic in the first night match on the main centre court.
Hewitt has been dogged by injuries in recent years and is entering the twilight of his career, but showed glimpses of the class that made him the world's best player in winning the invitational Kooyong tournament, beating Juan Martin del Potro in the final.
The 31-year-old, who has a history of titanic five-set battles on Rod Laver Arena, has already laid down a marker for the Tipsarevic match predicting it would go the distance.
"I haven't played him for a few years now," Hewitt said.
"But he's improved a bit in the last couple years obviously to get in the top-10. It's going to be a tough match obviously over five sets.
"I feel like all I can control is my preparation and doing all the right things. I've done absolutely everything in my power. I look forward to the challenge."
Women's second seed Maria Sharapova will actually open the tournament's proceedings on centre court against fellow Russian Olga Puchkova, while former French Open champion Li Na will meet Kazakhstan's Sesil Karatantcheva on Margaret Court Arena, the third showcourt at the sprawling tennis complex.
World number five David Ferrer, fresh off his record-equalling Auckland Open title on Saturday, does not get any respite from his trans-Tasman dash when he concludes the day's action on Hisense Arena against Belgium's Olivier Rochus.
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- Rod Laver Arena
- Lleyton Hewitt