The 2009 US Open Champion has struggled with wrist injuries since 2010 and had not played for over ten months.
Yet it appeared that Del Potro's injury jinx was behind him after reaching the quarter final of the Sydney International last week.
But the former world number four decided that the year's first grand slam had come too soon.
"It's a pity that I cannot take part in such an important tournament, yet this is another episode in the long way to recovery," Del Potro wrote on his Facebook account
. "I will follow the advice of my doctors and try to return as soon as possible."
Del Potro has slipped to 276 in the world rankings since injuring his left wrist in February 2014, but has indicated that he aims to play again in March, possibly in Miami or at Indian Wells.
"I appreciate the support that I received since I announced I was playing in Sydney," he added. "It was amazing."
This year's Australian Open has been hit by a series of exciting, big --hitting players either pulling out injured or struggling to reach peak fitness before the tournament begins Monday.
US Open champion Marin Cilic pulled out at the start of the year, as did Frenchman Jo-Wilfried Tsonga whilst Rafael Nadal has complained that he is still feeling the effects of an operation to remove his appendix.
The biggest uncertainly, however, concerns the fitness of Australia's Nick Kyrgios.
The teenage sensation arrived at Wimbledon an unknown but reached the quarter final after beating Nadal, announcing himself as one of the game's most exciting young talents.
Kyrgios has been desperate to get fit for his first 'home' grand slam since following his breakthrough season and had taken the past four months off to try and heal a persistent back injury that had cast doubt on his participation.
Last week it looked like he too might pull out but the 19-year-old confirmed he will be in Melbourne Monday.
"I'm obviously feeling it. It's not 100 per cent. But, you know, I'm good enough to compete," Kyrgios told the Sydney Morning Herald
on the eve of the tournament. "I'm noticing improvements every day ... Yeah, I think I'm ready to compete."