The Argentine last played on the ATP Tour when he retired from his opening match at the Dubai International in February and underwent surgery on his left wrist in late March.
Despite having a protected ranking of seventh in the world, the 26-year-old can only use it at a limited number of events and opted to take a wild card for the Sydney tournament, a warm-up for the Australian Open.
"I love playing in Sydney. The city and the fans are great and I can't wait to come back and defend my title," he said in a news release.
"Last year, I played some of my best tennis there and it is the perfect way to start the year. I am looking forward to being back in Sydney as it is one of my favourite cities to play."
After his triumph at Flushing Meadows in 2009, Del Potro's career was severely disrupted by surgery on his right wrist in 2010 before he battled his way back into the top 10 again.
His victory over local defending champion Bernard Tomic in the Sydney International final in January gave him his 18th career title.
(Reporting by Nick Mulvenney; Editing by John O'Brien)
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