The Australian Open champion lost his only previous head-to-head clash with Bellucci, but that was on clay back in 2009.
Wawrinka made a good start in the final grand slam of the year when he beat Jiri Vesely in straight sets in the first round on Monday, even if he was taken to a tie-break twice.
Bellucci also enjoyed a confidence-boosting start on the back of a strong service game to beat Nicolas Mahut 7-6 6-4 6-4.
Arthur Ashe Stadium will also host a potentially intriguing showdown between sixth seed Tomas Berdych and unseeded Australian Lleyton Hewitt.
Czech Berdych will be the favourite in the first round clash, but the 2001 champion Hewitt is likely to be a dangerous opponent, despite his 33 years.
In the women's draw, five-time grand slam champion Maria Sharapova meets Alexandra Dulgheru in the second round.
The fifth-seeded Russian showed no mercy in the first round as she took the final 10 games to beat compatriot Maria Kirilenko 6-4 6-0 and is expected to be just as ruthless against Romania's Dulgheru.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Greg Stutchbury)
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