Harrison, the 20-year-old world No.62, looked like a boy against a man as the Serbian top seed's march towards a potential third straight title at Melbourne Park gathered speed.
Djokovic could not have been more impressive, stamping his authority on the match from the start to win 6-1 6-2 6-3 and set up a third round meeting with Czech 31st seed Radek Stepanek.
Never stretched, the world No.1 allowed the young American just one point in the first three games and took just 20 minutes to claim the first set.
Harrison kept fighting, hoping Djokovic's superb form would tail off but it never dipped.
Even the American's powerful first serve couldn't dent the Serb's total control, Djokovic's return game exquisite while he gave up a remarkably-low eight points on his own serve for the match.
Harrison's frustration was made clear in the third set when, after pausing before serving to wait for some fans to be quiet, he called out: "It's already tough enough right now."
Djokovic, who won the Australian Open in 2008 as well as each of the past two years, will take a 16-match winning streak at Melbourne Park into his clash with Stepanek, who took a set off the Serb at Wimbledon last year but has lost their past six meetings.
Djokovic said Harrison had a bright future but his own ability to seize the early ascendancy made it tough for the youngster to find his best.
"When I was a set up after 25 minutes I had an important mental advantage, I felt comfortable," the Serb said.
Fellow Serb Janko Tipsarevic, the eighth seed, who beat Australia's Lleyton Hewitt in the first round, had a much tougher time of his second round match on Wednesday night, downing Slovakian Lukas Lacko 6-3 6-4 3-6 4-6 7-5.