But world No 1 expects to face tough opponents not least Victoria Azarenka, the world No 2, who beat her in Cincinnati final.
Serena Williams 'definitely ready' to defend her US Open tennis title
Williams is seeking her 17th grand slam singles crown and fifth US Open title, which would move her one shy of Chris Evert's Open-era record for most titles at the year's final major event on the Flushing Meadows hardcourts.
"I'm definitely prepared. I'm definitely ready for New York," Williams said. "I definitely had more matches than I could want, but I'm definitely prepared for the US Open."
The 31-year-old American has been on an amazing run over the past 14 months, going 77-4 and capturing last year's Wimbledon, London Olympic and US Open titles, plus this year's French Open crown.
But two of those defeats came at the hands of Azarenka, in last February's Doha final and last Sunday at the WTA final in Cincinnati by 2-6, 6-2, 7-6.
It was only the third victory for the 24 year old from Belarus over Williams but with the two having won seven of the past nine grand slam titles, it sets the stage for a potential rematch of last year's US Open final.
"It would be totally different circumstances," said Williams, who also beat Azarenka in this year's Rome final. "It's just a new event. You just got to go in there with a fresh mind."
And without a win streak such as she had the past few grand slam events.
"It makes me more relaxed and almost happy that I lost because now I don't have to worry about every day someone asking me about some silly winning streak," Williams said. "So maybe it was for the best."
Williams also finds herself in a cordial rivalry, appreciating Azarenka off the court as a friend and on the court as an adversary.
"She's so competitive on the court, like an animal, and I'm the same exact way, like my dad described me as a pitbull," Williams said.
Williams is looking for her ninth title of the year after triumphs at Brisbane, Miami, Charleston, Madrid, Rome, Roland Garros, Bastad and Toronto.
But she has proven vulnerable in grand slam tournaments, falling to compatriot Sloane Stephens in the Australian Open quarter-finals and Germany's Sabine Lisicki in the fourth round at Wimbledon, but completing her title run on Paris clay with a victory over US Open third seed Maria Sharapova of Russia.
Azarenka, the reigning Australian Open champion, says she has learned from past losses to Williams.
"Every time we play, I face a big challenge, my biggest opponent, and that's what I want to go through," Azarenka said.
"I had tough losses before against her, but I feel like I learned from those losses, and it helps me improve. I feel like I'm playing better and better. I'm reaching for the new level that I want to be at, physically, mentally, tennis-wise and that's the progression that I'm really the most excited about."
Azarenka took confidence from rallying to beat Williams in the Cincinnati final, but says the American will be the favourite on home soil.
"I will not be a favourite," Azarenka said. "She is No 1 in the world. She is a great champion, and she's defending champion, so she's going to be a favourite.
"About who's second favourite, third favourite, I don't really care about that. But I think it's a great boost of confidence to go to the US Open, great week to go through matches back to back. Tough matches are also important for me to feel like I'm back competing at the same level constantly and consistently. So that's what I'm most excited about."
Sharapova, the four-time grand slam winner, who split with coach Jimmy Connors after losing their only match together in her Cincinnati opener, has not played another match since a second-round Wimbledon exit due to a left hip injury.
Follow us @SprtNationalUAE