Also coming back from injuries are 2014 champion Stan Wawrinka (knee), big-serving Canadian Milos Raonic (calf and wrist), and world number one Rafael Nadal (knee).
Twelve-time Grand Slam winner Djokovic beat world number five Dominic Thiem in straight sets in the Kooyong Classic this week.
Surprise Paris Masters winner Jack Sock may have to overcome Kevin Anderson (11) or Lucas Pouille (18), as well as Philipp Kohlschreiber (27) if he is to reach the quarter-finals.
Wawrinka has been battling a knee injury and has not played since he was knocked out in the first round of Wimbledon last year, and the Swiss was one of the major question marks heading into the Jan. 15-28 Australian Open.
The Spaniard is set to face Damir Dzumhur in the third round, John Isner in the fourth and Marin Cilic in the quarter-finals - if the seedings work out.
"I'm really, really happy to be back on the Tour and seeing the sun", Wawrinka told reporters after an event with the tournament's ball kids at Melbourne Park on Tuesday.
Qualifying is free to attend, but with no matches underway due to wet weather, the crowd quickly made their way to the show court.
Brother Mischa (32) and Albert Ramos-Vinolas (21) should not unduly trouble the 20-year-old, but six-time champion Djokovic, seeded 14th after his lengthy absence from the tour, could yet blow his portion of the draw wide open should he prove his fitness.
However, he has to improve on his consistency at the highest level and the Australian Open would be a good chance.
Goffin enjoyed a strong finish to 2017, reaching the decider of the ATP Finals and the Davis Cup final with Belgium.
A lacklustre Thiem lost the first set to a rampant Djokovic before improving in second for a 6-1 6-4 scoreline. Has two career wins over Rafael Nadal.
The 23-year-old Austrian finished the 2017 season with a title on clay in Rio de Janeiro and a year-end fifth ranking.
But he has already had a rough start to the season - pulling out of the Qatar Open semi-final with flu, losing to Novak Djokovic at Kooyong before pulling out as with the same virus, disrupting the world number five's build-up to the Australian Open.
Roger Federer will open his title defence against Slovenia's Aljaz Bedene and has a potential quarterfinal with David Goffin in the Australian Open.
"I don't usually like going to draws, I just want to see the sheet". He eventually went down to Nadal but showed enough spunk to be noticed.