Belarussia’s Victoria Azarenka, who beat Williams in Sunday’s final of the Cincinnati Open, is the second seed ahead of Maria Sharapova of Russia and Poland’s Agnieszka Radwanska.
Williams heads into the Open, which starts on August 26, looking to add to her French Open title from this year, her 16th Grand Slam singles triumph, which includes four championships at Flushing Meadows.
Williams’ sister Venus, a two-time US Open winner but currently ranked 60th in the world, was unseeded.
Serbia’s Novak Djokovic is the top seed in the men’s draw which includes five-time US Open champion and 17-time Grand Slam winner Roger Federer as seventh seed – his first time the Swiss has been placed outside the top three in a Grand Slam in over ten years.
Spaniard Rafael Nadal is the number two seed, ahead of Britain’s Andy Murray, the defending champion and this year’s Wimbledon winner.
The draw for the tournament will be held on Thursday.