American Williams remains in the running for a sixth title having seen off compatriot and wildcard Townsend 6-3 6-1 in less than an hour under lights at Arthur Ashe Stadium.
The number one seed will meet another American - Vania King - in the second round after proving too strong for world number 103 Townsend.
Williams won all but two first service points and broke her opponent twice on her way to taking the opening set in just 29 minutes.
The second set was even more brief as the world number one wasted no time in wrapping up victory.
Williams made only three unforced errors in the second set - again breaking twice as Townsend was overpowered by the 17-time major champion.
The 18-year-old managed to win just one of three service games as she struggled to cope with the quality of her opposition, while Williams booked a second-round meeting with King.
World number 81 King saw off Italy's Francesca Schiavone in three sets to ensure her progression earlier on Tuesday.