The 31-year-old Argentinian, who made the last eight at Melbourne Park in 2009 and 2012, has not played since slipping and hurting his knee on the grass in the Wimbledon tune-up at Queen's in June.
At the tournament past year, Andreescu was a qualifier and lost in the second round before going off to conquer the tennis world and win the U.S. Open.
"It was an exceptionally intense choice to make as I love to play in Melbourne however I need to regard the recovery plan for my knee and body".
Andreescu, the world number six, injure her knee at the season-ending WTA Finals in Shenzhen, China, ending an unbelievable year for her. In his Twitter she wrote that she did not have time to recover, as the Australian Open is too soon.
Bianca Andreescu, of Canada, holds up the championship trophy after defeating Serena Williams, of the United States, in the women's singles final of the U.S. Open tennis championships Saturday, Sept. 7, 2019, in NY.
Del Potro has played just one Australian Open since 2015, reaching the third round two years ago.
"I can't wait to come back to Aus soon", she said.
The Australian Open will run from January 20 to February 2.
Andreescu suffered her knee injury three games into her match against Karolina Pliskova at the WTA Finals in Shenzhen, China, in October, and eventually retired.