The tournament got off without a hitch Monday, despite the wrath of Hurricane Irene lashing the East Coast, including New York City, over the weekend.
The former world No. 1 Williams, a two-time U.S. Open champ and two-time runner-up, breezed past Russia's Vesna Dolonts, 6-4, 6-3 under the lights at Arthur Ashe Stadium.
"We weren't expecting a hurricane to come through," Williams said. "Where I'm from hurricanes do happen down in Florida, but I'm glad tennis was able to be started today."
Unseeded at the U.S. Open this year, Williams moved to 51-3 all-time in first- round grand slam matches. That includes 20 straight such victories. She also earned her 60th U.S. Open victory. Only Chris Evert (101), Martina Navratilova (89), Steffi Graf (73) and Lindsay Davenport (62) have more wins.
Williams, who also moved two triumphs within 600 for her career, hadn't played since a fourth-round loss at Wimbledon. She withdrew from events in Toronto and Cincinnati due to a viral illness.
The third-seeded Sharapova was tested mightily in a 3-6, 7-5, 6-3 come-from- behind victory over Britain's Heather Watson at Ashe Stadium. The tall Russian needed 2 hours, 34 minutes to reach the round of 64.
The promising 19-year-old Watson was up a set and then broke Sharapova to open the second, but the Russian star broke right back to mount her comeback on Day 1.
A sloppy Sharapova tallied eight double faults and a whopping 58 unforced errors, but also struck 32 more winners (41-9) than the young Watson.
The 24-year-old Sharapova has now won her last six matches overall, including a hardcourt title in Cincinnati two weeks ago.
Sharapova is a former world No. 1 and three-time Grand Slam champion, including a U.S. Open titlist back in 2006. She was last month's Wimbledon runner-up to Kvitova.
The second-seeded 2010 U.S. Open and Wimbledon runner-up Zvonareva zipped past France's Stephanie Foretz Gacon 6-3, 6-0 at Armstrong Stadium.
The Russian Zvonareva was dismantled by Kim Clijsters, 6-2, 6-1, in last year's lopsided U.S. Open finale.
Meanwhile, 22-year-old Romanian Alexandra Dulgheru, ranked 48th in the world, stunned the fifth-seeded Kvitova 7-6 (7-3), 6-3 at the USTA Billie Jean King National Tennis Center. Kvitova piled up 52 unforced errors en route to her early exit.
Since upending Sharapova in last month's Wimbledon finale, Kvitova has gone just 2-3 overall.
No. 12 seed Agnieszka Radwanska beat her younger sister, Urszula Radwanska, 6-2, 6-3. Urszula Radwanska is 2-8 in her career vs. top 15 players with her only two wins coming against her sister at 2009 Dubai and No. 8 Svetlana Kuznetsova at 2009 Indian Wells.
Thirteenth-seeded Chinese Peng Shuai doused American Varvara Lepchenko 6-3, 6-4; 14th-seeded Slovakian Dominika Cibulkova dismissed Chinese Zhang Shuai 6-3, 6-4; 19th-seeded Julia Goerges leveled fellow German Kristina Barrois 6-3, 6-2; 24th seed Nadia Petrova of Russia topped Taiwan's Yung-Jan Chan, 6-3, 1-6, 6-4; 25th seed Maria Kirilenko of Russia topped fellow countrymate Ekaterina Makarova, 4-6, 6-1, 7-6 (7-3); and 27th-seeded Czech Lucie Safarova overcame Slovakian Magdalena Rybarikova 2-6, 6-3, 6-2.
Sixteen-year-old Madison Keys dismissed 37-year-old Jill Craybas 6-2, 6-4 in an all-American affair.
"This is my first time in the main draw here, and obviously it was a good first day," said the big-hitting Keys.
Ukrainian Kateryna Bondarenko also advanced and will meet Zvonareva in her next outing.
The top seed is last week's New Haven titlist Caroline Wozniacki, the 2009 U.S. Open runner-up to Clijsters, who had won the last two titles in Flushing but is missing this year's fortnight because of injury.
This year's U.S. Open singles champ will pocket at least $1.8 million, and U.S. Open Series winner Serena Williams, seeded 28th, has a shot at earning a record $2.8 million in the Big Apple. The three-time U.S. Open titlist Serena has won her last 12 matches overall and is considered one of the favorites in New York.