The tall Argentine lost a year of his career to a wrist injury after winning the US Open in 2009 and since his return, has failed to rediscover the heights of form he reached at Flushing Meadows three-and-a-half years ago.
On Tuesday, the sixth seed beat qualifier Adrian Mannarino 6-1 6-2 6-2 to reach the second round, an improvement on the four sets he took to beat the Frenchman at the same stage last year.
"I played really well," he said. "I remember last year when we played the first round also, and he had a better match than today.
"But I think I played really aggressive. I made a lot of winners with my forehand. I served well. I made very good start to this Open."
Despite his good start and the absence of the injured world number four Rafa Nadal, Del Potro was not confident of emerging from a half of the draw which also includes Roger Federer and the newest member of the Grand Slam winner's club, Andy Murray.
"They are so far from me at the moment," he added. "We play five sets and matches can be tough for all the players, so I (am) just thinking about my second round.
"Hopefully I can go far, but I need to play better and better.
"I think the favourites are the same even if Rafa is not here. If Rafa was here, he would be a favourite for sure also. But Roger, Novak, Andy Murray, and other guys are the favourites to win the tournament."
Del Potro will face Germany's Benjamin Becker in the second round on Thursday.
Still only 24, he reached the quarter-finals at three of the four Grand Slams last year, including at Melbourne Park, but he knows from experience what it takes to go those extra three steps.
"I'm here trying to do that, but it's not easy," he said. "I know how tough it is to win a Grand Slam. But I also know the way to win a Grand Slam.
"So I'm trying to do that for this year. Could be my biggest challenge this year, to win another Grand Slam. But they are playing really good tennis, and it's not easy."
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- Adrian Mannarino