Nadal dominated the singles charts with 7,660 points, and Halep remained No. 1 in the WTA rankings despite being down with a back injury.
Simona Halep had pulled out of last month's China Open and withdrew from this week's Kremlin Cup because of the persistent problem.
Simona Halep played two Grand Slam finals winning the French Open crown and won titles in Shenzhen and Montreal.
Roger Federer remains behind Nadal with 6,900 points. And in the WTA rankings, Japan's Naomi Osaka jumped two positions to the fourth spot.
Simona Halep said that she was "worried now" after a persistent back problem forced her out of the China Open after just 31 miserable minutes.
The French Open champion suffered a back injury during a practice session on Sunday and failed to fully recover for her opening match in Wuhan.
Romania's Simona Halep continued to lead Women's Tennis Association (WTA) rankings released on Monday, ahead of Denmark's Caroline Wozniacki.
Williams can match Margaret Court's all-time record of 24 majors with another title at Flushing Meadows.
It was a second straight first-round exit at Flushing Meadows for Romania's Simona Halep, who dropped her opening match to Maria Sharapova last year.
Kiki Bertens defeated the world number one Simona Halep 2-6, 7-6 (8/6), 6-2 in the Cincinnati WTA final.
Roger Federer will be bidding to increase his tournament leading total, while Djokovic is keen to win the only Masters 1000 tournament missing from his trophy collection.
Rafael Nadal withdrew from next week's ATP Cincinnati Masters event as he prepares for the US Open.
In a gruelling 2hr 41min battle, French Open champion Halep prevailed 7-6 (8/6), 3-6, 6-4 over Stephens in a repeat of the duo's meeting in the final of Roland Garros earlier this year.
American third seed Stephens surged into Sunday's final against world number one Halep after overpowering Svitolina 6-3, 6-3 in the day's second semi-final.
The top-seeded Halep hammered 19 winners and won 77 percent of points on her first serve in the 88-minute contest.
Top seed Halep took no prisoners against Williams, blitzing the 38-year-old American 6-2, 6-2 in just 71 minutes to reach the quarter-finals.
Romania's Simona Halep continued to lead the Women's Tennis Association rankings released on Monday with 7,511 points, followed by Denmark's Caroline Wozniacki.