As the greatest player of her generation, Williams is the obvious choice to win the women's singles tournament, starting on Monday, but faces challenges on several fronts including the calendar. (Agencies)
If she wins, the 31-year-old American will be the oldest woman champion since tennis turned professional in 1968 but time has not caught up with Williams just yet.
"I'm definitely prepared. I'm definitely ready for New York. I'm looking forward to it," she said.
"I feel like I definitely had more matches than I could want, but I'm definitely prepared for the US Open," she added.
The American is already the second oldest grand slam winner after she won last year's US Open and has captured eight titles this season, including the French Open. But not everything has gone her way.
A quarter-final loss to Sloane Stephens at the Australian Open and a fourth-round defeat to Sabine Lisicki at Wimbledon were followed by her gut-wrenching loss to Victoria Azarenka at the Western and Southern Open in Cincinnati earlier this month.
Williams seemed to have the match under control when she cruised through the opening set only to lose in a third-set tie breaker, boosting Azarenka's confidence heading into the year's final grand slam.
The pair are seeded one and two and are drawn to meet in the final, just as they did last year. Williams beat Azarenka 7-5 in the final set 12 months ago but remains aware of the danger posed by the Belarusian.
"I'm a big Victoria fan. I think she's just the ultimate competitor on the court and just really nice," Williams said.
The 24-year-old Azarenka won her second consecutive Australian Open this year and is perfectly suited to the unforgiving hardcourts at Flushing Meadows.
One of the few players who is unafraid of slugging it out with Williams in the cauldron-like atmosphere of Flushing Meadows, Azarenka looms as the obvious danger in what has all the makings of a great rivalry.
"Every time we play, I face a big challenge, my biggest opponent," Azarenka said.
"Playing in the final of any tournament against the best player, that's what you really strive for and to overcome and beat. I've had tough losses before against her but I feel like I learned from those losses, and it helps me improve," she said.
The chances of the pair meeting in the final have increased since the withdrawal of Maria Sharapova, because of injury, and the shock retirement of Wimbledon champion Marion Bartoli but there are plenty of other dangers lurking in the draw.
As the greatest player of her generation, Williams is the obvious choice to win the women's singles tournament, starting on Monday, but faces challenges on several fronts including the calendar.