The SAR player, ranked 94th in the world, was ousted in a 7-6, 1-6, 3-6, 3-6 loss to his 20th seeded opponent at Louis Armstrong Stadium.
Wong hit the ground running in the early going, serving nine aces while taking advantage of aggressive play from Paul for a 7-3 win in the opening set tiebreak.
However, the American quickly found his footing the rest of the way, hitting 40 winners to wrap up victory in 2 hours and 43 minutes.
Defeat marks an impressive run of form for Wong, who won all three of his qualifying matches to enter the main draw at the final Grand Slam of the year for the second year running.
Wong, 22, last year became the first male player from the SAR to compete in a Grand Slam main draw by reaching the third round of the US Open.
