The Williams sisters, with six U.S. Open singles titles between them, posted first-round victories on Monday.
Top seed and four-time titlist Serena Williams dismantled Italian Francesca Schiavone, the 2010 French Open champion, 6-0, 6-1 in one hour. Serena, the reigning U.S. and French Open champ, won the first 10 games of the match and took advantage of eight double faults.
"I'm really excited. I know playing a former Grand slam champion in the first round was a tough draw, but I knew I had to be super serious," Serena said following her match.
She finished off Schiavone just in time, as it started raining when the players were coming off the court.
Serena beat reigning Australian Open queen Victoria Azarenka in last year's final in New York. The 16-time Grand Slam titlist is a two-time runner-up in Flushing.
The 33-year-old Venus, a two-time champion and former world No. 1, leveled 12th-seeded surprise Wimbledon semifinalist Kirsten Flipkens, of Belgium, 6-1, 6-2 in 1 hour, 24 minutes at Arthur Ashe Stadium.
The currently 60th-ranked seven-time Grand Slam champion Venus captured the Open back-to-back in 2000 and 2001 and was the runner-up here in 1997 and 2002. Her second-round opponent will be China's Zheng Jie.
"I stay positive because I know I can play great tennis," said Venus, who has been slowed by a lower back injury this year. "Sometimes you just have to go through more than what you want to go through. Sometimes you have to have losses. When I had losses, it always motivates me a lot to do better and to work harder."
Meanwhile, third seed Agnieszka Radwanska and fifth-seeded Chinese star Li Na were also among the winners on Day 1.
The 2012 Wimbledon runner-up Radwanska, of Poland, routed Spaniard Silvia Soler-Espinosa 6-1, 6-2 at Ashe, while this year's Australian Open runner-up and the former French Open champion, Li, leveled Belarusian Olga Govortsova 6-2, 6-2 on the grounds at the USTA Billie Jean King National Tennis Center.
Up next for Radwanska will be Spaniard Maria-Teresa Torro-Flor, while Li will encounter Swede Sofia Arvidsson.
Eighth seed Angelique Kerber of Germany routed Czech Lucie Hradecka, 6-1, 6-1; and No. 9 seed Jelena Jankovic of Serbia topped American Madison Keys, 6-3, 6-4. The former world No. 1 Jankovic was the 2008 U.S. Open runner-up to Serena.
Rising 15th-seeded American Sloane Stephens advanced by outlasting a game Mandy Minella, of Luxembourg, 4-6, 6-3, 7-6 (7-5), on Monday. The 20-year-old Stephens, who overcame 55 unforced errors, reached the semifinals at the Aussie Open and quarterfinals at Wimbledon this year.
"That many, that's horrible," Stephens said of her miscues. "But I think I was just so nervous, I was so tight, and I couldn't really get a grip. But I thought I managed to play some good points and kind of like get loose. I thought that's what helped me the most."
Also, 16th-seeded Wimbledon runner-up Sabine Lisicki, of Germany, handled Russian Vera Dushevina 6-2, 7-6 (7-3); 18th-seeded Spaniard Carla Suarez Navarro dismantled American Lauren Davis 6-0, 6-0; 19th-seeded Romanian Sorana Cirstea edged out Canadian Sharon Fichman 7-5, 5-7, 6-1; and 23rd-seeded American Jamie Hampton bested Spaniard Lara Arruabarrena 6-4, 6-2 for her first-ever U.S. Open match win.
Some other seeded winners on Monday were No. 24 seed Ekaterina Makarova, No. 25 Estonian Kaia Kanepi, No. 30 Brit Laura Robson and No. 32 Russian Anastasia Pavlyuchenkova. Kanepi overcame American Vania King in three sets, 4-6, 7-6 (7-4), 6-1.
A mild upset came when Austrian Patricia Mayr-Achleitner doused 29th-seeded Slovak Magdalena Rybarikova, 7-6 (7-2), 6-3.
Also advancing was American Coco Vandeweghe, who topped Serb Aleksandra Krunic 6-4, 7-6 (7-5).