NEW YORK -- Venus Williams had been 14-0 in the first round of the U.S. Open, though she never had to face an opponent ranked in the top 30 at that stage.
Williams was usually the seeded player, but after two years of illness and injury, the seven-time major champ was the one pulling the upset Monday when she defeated Wimbledon semifinalist Kirsten Flipkens.
Her ranking down to 60th, Williams beat the 12th-seeded Flipkens 6-1, 6-2 for one of her biggest wins since she pulled out of this tournament two years ago because of Sjogren's syndrome, an autoimmune disease.
The 33-year-old looked strong Monday, fighting off three break points at 2-2 in the second set in a game that went to six deuces.
Bothered by a lower back injury, Williams was playing just her third event since a first-round loss at the French Open. She hadn't defeated a top-20 opponent since last October.
Flipkens, meanwhile, had been enjoying a career year. The Belgian had never reached the round of 16 at a major tournament before the Australian Open, then made her run at Wimbledon.
In the day's first big upset, a British man not named Andy Murray -- 179th-ranked qualifier Daniel Evans -- stunned 11th-seeded Kei Nishikori in straight sets. Evans won 6-4, 6-4, 6-2 in his U.S. Open debut.
Both are 23, but Nishikori was playing in his 17th Grand Slam event, with a 25-16 record coming in. Evans was 0-2, both matches at Wimbledon.
"I was pretty calm today," Evans said. "It wasn't that much of a big deal what was happening on the court. I wasn't nervous serving it out."
Third-seeded Agnieszka Radwanska and fifth-seeded Li Na advanced in straight sets on the women's side. Radwanska beat Silvia Soler-Espinosa 6-1, 6-2, while Li defeated Olga Govortsova 6-2, 6-2.
Radwanska withdrew from her last tournament at Cincinnati on Aug. 15 before her quarterfinal against Li to fly home for her grandfather's funeral.
"Sometimes there are some things more important than tennis," Radwanska said. "It was something like that, and it was really a pretty quick choice. Of course, this is the situation that we have to be home for the family, and I think I owed my granddad to be there."
American teen Lauren Davis lost by a "double bagel," falling to 18th-seeded Carla Suarez Navarro of Spain 6-0, 6-0 in 57 minutes.
The day started with some big news from a veteran U.S. player: Three-time Grand Slam quarterfinalist James Blake announced he would retire after the tournament at age 33.
Roger Federer is 32, and his struggles this year have him hearing questions about how much longer he'll play. The five-time U.S. Open champ is seeded seventh, his worst since 2002.
Federer plays Grega Zemlja in Monday's last match at Arthur Ashe Stadium. Top-seeded Serena Williams begins the night session against Francesca Schiavone. Rafael Nadal was facing doubt about his career when a knee injury sidelined him for seven months. But with a 10-0 record on hard courts leading to the U.S. Open, he's seeded second. The Spaniard opened against American Ryan Harrison.