Second and third seeds Jelena Jankovic and Daniela Hantuchova were sent spinning from the Amelia Island tennis championship on Friday.
Compatriot Elena Dementieva added her name to the tournament's lengthy casualty list when she withdrew with a left thigh muscle injury.
Serena, a six-times champion in New York who is seeded 17th, will start her campaign against Polish world number 60 Magda Linette and could face Venus in the third round before a possible fourth-round showdown with Romanian top seed Halep.
Justine Henin beat third seed Jelena Jankovic 7-6, 7-5 to capture her second Toronto Cup.
A Henin and Jankovic final may lack the pizzazz of a Maria Sharapova-Serena Williams showdown but their records this season are second to none, with the battling Belgian claiming five titles and the Serbian four.
World number one Justine Henin and second seed Jelena Jankovic refused to be blown off course by recording quarter-final wins on a wild and windy day at the Toronto Cup on Friday.
The world number one beat China's Peng Shuai 7-5, 6-2 in the third round.
Maria Sharapova pulled out before her Los Angeles Classic semi-final against Nadia Petrova with a strain in her lower left leg.
Second seed Jelena Jankovic outlasted Victoria Azarenka 6-4, 6-7, 6-2 to reach the semi-finals of the Los Angeles Classic on Friday.
US Open champion Sloane Stephens said she has no pity for Madison Keys after thrashing her 6-3, 6-0 in Saturday's final, given the huge runnersup check her friend will receive.
Novak Djokovic summoned some cinematic inspiration to help him conquer grand slam king Roger Federer and silence the roaring supporters of the Swiss at Sunday's US Open men's final.
Top seed Amelie Mauresmo and third seed Maria Sharapova also marched on with straight-sets victories at the US Open.\n
IMAGES from the matches played at Miami Miasters in Key Biscayne, Florida, on Wednesday
Following is a list of American Serena Williams' 22 grand slam singles titles as she equalled Steffi Graf's professional era record with victory at Wimbledon on Saturday
Russia's Anna Chakvetadze beat injury-hit top seed Jelena Jankovic of Serbia to win the women's title at the Den Bosch Open on Saturday, while Croatia's Ivan Ljubicic beat Dutchman Peter Wessels to win the men's.
Former world number one Martina Hingis was knocked out by Jelena Jankovic at the Sydney International.
Jelena Jankovic finally ended a losing run against Maria Sharapova to claim her first grasscourt title.
The Indian ace was shown the door by the eighth seeded Italian in the second round of the Birmingham DFS Classic.
Top seed Jelena Jankovic of Serbia and third-ranked Slovak Daniela Hantuchova enjoyed contrasting opening-round victories in the Auckland Classic on Tuesday.
Ana Ivanovic beat the Russian 6-2, 6-1 the enter the French Open final.
The former Wimbledon and US Open runner-up was given a free-ride into the first Grand Slam of the year.
Novak Djokovic beat Russia's Igor Andreev 6-3, 6-3, 6-3 to reach the semi-finals of a Grand Slam tournament for the first time.
Maria Sharapova made it to her maiden semi-finals of the French Open by beating fellow Russian Anna Chakvetadze 6-3, 6-4.
Jelena Jankovic beat Czech Nicole Vaidisova while Ana Ivanovic upset 2006 runner-up Svetlana Kuznetsova.
Williams surrendered her Wimbledon crown last July when she lost to the 22-year-old Serb in the third round.
Jelena Jankovic continued her impressive preparation for the French Open when she beat world number three Svetlana Kuznetsova 7-5 6-1 in the final of the Italian Open on Sunday.
Third seed Jelena Jankovic continued her good form on clay when she swept aside former French Open finalist Elena Dementieva 6-2 6-1 to reach the semi-finals of the Italian Open on Friday.
World number one Justine Henin of Belgium fought back from the brink of defeat to reach the semi-finals of the German Open today, beating fifth-seeded Serbian Jelena Jankovic.
The third seeded Russian rallied to beat the American to reach the semi-finals of the Warsaw Cup.
Justine Henin beat Italian Mara Santangelo 6-2, 6-1 in the quarterfinals of the Warsaw Cup.
Unseeded Venus Williams marched into the Family Circle Cup semi-finals by beating Spain's Anabel Medina Garrigues 6-4 7-5 on Friday.
Top seed Nadia Petrova made short work of China's Zheng Jie with a 6-2, 6-3 victory to move into the quarter-finals of the Amelia Island championship on Thursday.
Top seed Justine Henin rallied from a set down to beat Jelena Jankovic and reach the final of the Qatar Open.
Justine Henin knocked out Swiss Patty Schnyder 3-6, 6-4, 7-5 to reach the Qatar Open semi-finals.
Amelie Mauresmo reached the Dubai Open final after Serbia's Jelena Jankovic retired through injury when trailing 6-2 on Friday.
The rising Serbian star beat Martina Hingis 7-6, 6-2 to reach the semi-final of the WTA Dubai Open.
Andy Roddick and Serena Williams scored contrasting wins to enter the Australian Open quarterfinals.
The world No 32 cited a left wrist injury as the reason for her withdrawal.
Serena Williams will be 'ready to go' when she returns to action this week in the United States' Fed Cup first round tie against the Netherlands, captain Kathy Rinaldi said on Wednesday.
The Belgian saved a match point before beating the Serb in the final of the Sydney International.
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