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 No. 60, 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.
"For me, I stay positive because I know I can play great tennis," Williams said. "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."
ACE™ Brand Pressure Point of the Match: Having just surrendered a break-of-serve lead in the second set, Venus fought off three break points at 2-2, the final when Flipkens hit a forehand out. Venus would go on to hold the six-deuce game and wouldn't lose a game thereafter.
The 33-year-old looked strong Monday, purple braids poking out of her visor that matched her floral dress. Williams fought 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.
"I realize that I haven't had a lot of chances to play this year or a lot of chances to play healthy this year, have had injuries and what have you," she said. "So I'm just going to have to keep working my way into it maybe more than some of the other players. But I know I can do that."
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.
Rafael Nadal's stay at Wimbledon ended in his opener. In his first Grand Slam match since -- and first U.S. Open since 2011 -- the second-seeded Spaniard rolled past American Ryan Harrison 6-4, 6-2, 6-2. Nadal, who missed last year's tournament because of a left knee injury, improved to 16-0 on hard courts this year.
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."
Radwanska withdrew from her last tournament at Cincinnati on Aug. 15 before her quarterfinal against Li to fly home for her grandfather's funeral.
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.
No. 16-seeded Sabine Lisicki, the Wimbledon runner-up, beat Vera Dushevina 6-2, 7-6 (3), while 23rd-seeded American Jamie Hampton defeated Lara Arruabarrena 6-4, 6-2.
On the men's side, eighth-seeded Richard Gasquet eliminated American Michael Russell 6-3, 6-4, 6-2. Bernard Tomic rallied past Albert Ramos in five sets, winning 6-3, 3-6, 4-6, 7-6 (1), 6-3 in nearly four hours.
The day started with big news from a veteran U.S. player: Three-time Grand Slam quarterfinalist James Blake said 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.