The 12-times Grand Slam champion, seeded an unfamiliar 14, was too strong for American Donald Young, winning 6-1, 6- 2, 6-4 in 1hr 51min on Margaret Court Arena.
The Serbian former world number one has been out of action for six months.
But he looked in good shape as he worked his way into the second round where he will play either France's Gael Monfils or Spanish qualifier Jaume Munar.
Djokovic, wearing a flesh-coloured protective guard on his right serving elbow, saluted the cheering crowd as he won on his sixth match point.
"There is no better place to start than here in Australia, I love coming here, I love playing here," Djokovic told the crowd.
"It's been a long period without any official matches but I spent as much quality time as I could with my family.
"I wanted to start with the right intensity, which I have, I played perfect tennis in the first couple of sets and Donald came back in the third set.
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