Both Williams and her first round opponent, Francesca Schiavone, will be making their 53rd major appearance next week, a figure only bettered by three other active players.
Williams arrives in New York in a rich vein of form, having won 14 of her past 15 matches, picking up the Emirates Airline US Open Series title in the process. Should she make her way past Schiavone, the draw has presented her with the opportunity to exact revenge on Sloane Stephens, who tripped her up at this year's Australian Open.
Leading the way in the bottom half is No.2 seed and last year's runner-up Victoria Azarenka. After scoring a rare triumph over Williams in the Cincinnati final on Sunday, Azarenka will go into her opening round against Dinah Pfizenmaier brimming with confidence; lurking further down the line are Dominika Cibulkova, Ana Ivanovic, Petra Kvitova and 2011 champion Samantha Stosur.
Maria Sharapova's late injury withdrawal promoted Sara Errani to the No.4 seed berth and she will start against Ayumi Morita. The other leading seeds in her quarter are Caroline Wozniacki, Roberta Vinci and Maria Kirilenko.
First round action at Flushing Meadows begins on Monday, with the final scheduled, for the first time in the tournament's 133-year history, to take place on the second Sunday of the fortnight.