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.
It was an impressive performance, with the Serb breaking Young's left-handed serve six times, hitting 33 winners and conceding only 27 unforced errors.
"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."
Wawrinka wins on return from injury
Stan Wawrinka struggled at times in his first match since last year's Wimbledon, but held on to beat Lithuania's Ricardas Berankis 6-3, 6-4, 2-6, 7-6 (2) in the first round of the Australian Open.
The 2014 champion only connected on 50 percent of his first serves and was broken four times in the match. He also looked physically spent toward the end of the fourth set before rallying to dominate the tiebreaker and close out the match.
Wawrinka underwent surgery on his left knee after Wimbledon and didn't play another match in 2017. He delayed his comeback at the start of this season by pulling out of a couple exhibitions before the Australian Open and made a last-minute decision to take part in the tournament.
"I'm proud to be back already," he said after his match. "Honestly, to win today, it means a lot for me."
The ninth-seeded Swiss player is also playing without a coach after splitting with long-time coach Magnus Norman in October....