Twice defending champion Djokovic will meet Harrison - for the third time in their careers - on Rod Laver Arena, and said after his first round victory over Paul-Henri Mathieu that he felt he knew the American's game and how to beat him.
Harrison, however, underwent intensive training, physical conditioning and scientific physiological testing during the off-season in order to help take his game to the next level.
He was told to lose weight in order to ensure he was more effective right to the end of long matches and how to manage his nutrition better and his first round win over Santiago Giraldo had given him confidence to press on against the Serb, he said.
"It's an opportunity. I have confidence in myself after all the work I have done during the off season," Harrison said ahead of the Djokovic clash.
"I feel different this year, mentally and physically I have put myself into a position where I feel that I'm going to go forward.
"I know that I've got myself into a better condition where I will be stronger and faster than the last time we played (in the second round at Wimbledon last year).
"On top of that I'm going to try and play my game... try to control my side of the net... and not get caught up in the hype of the situation and how good he is."
Women's second seed Maria Sharapova, who recorded a 6-0 6-0 victory over Russian compatriot Olga Puchkova in the first round, will meet Japan's Misaki Doi on Hisense Arena and could set up a third-round clash with Venus Williams.
Venus will meet France's Alize Cornet on Rod Laver Arena before Djokovic meets Harrison, so the tall American will undoubtedly know that a victory over the Frenchwoman will guarantee one of the matches of the third round.
Local hopes will be concentrated solely on the shoulders of women's ninth seed Sam Stosur, who nervously battled into the second round after a disrupted build-up.
The Australian meets China's Zheng Jie, who beat the 28-year-old in the first round of the Sydney tournament the week before the season-opening Grand Slam.