Both players head into tomorrow's contest as former champions at Flushing Meadows.
The match also holds extra significance following Roddick's recent announcement that he is to retire at the conclusion of his campaign in New York.
"I know this is special, this day, for him, but I'm doing my job," said Del Potro. "I will try to be focused on my match and doing my things, my shots.
"The match is going to be very tough. But, anyway, if I play in high level, it will be tough for both players.
"The crowd loves Andy here and they have respect me, so it will be a fantastic show to the players and to the fans also."
Del Potro won the title in 2009, while Roddick emerged victorious in 2003.