The world number one is aiming to win the event at Flushing Meadows for the third year in a row - the first time she will have achieved a hat-trick of grand slams in the same tournament in consecutive attempts.
Her bid began in style with an ominous display to see off teenager Townsend 6-3 6-1 to progress in just 55 minutes.
Williams has endured disappointment in the three grand slam events so far this year, with the 32-year-old's run to the fourth round of the Australian Open as good as it has got.
The 17-time singles grand slam winner has not lost her appetite for success, though, and is relishing the opportunity to triumph on home soil yet again.
"I just come out and play. This was the first slam I won and I love to come back. I never want to stop." she said.
Williams also predicted a bright future for American tennis, with big things expected of the likes of Townsend and Madison Keys.
"Taylor's incredibly talented. She's such a great person, I love her and I love that there's so many great Americans," she said.
"We have such a great future and we have so much to look forward to."