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.
Spain's Fernando Verdasco came back from the brink of defeat to beat the top seed 6-7, 7-6, 6-4 in the last 16 of the Rome Masters.
John Isner pushed on towards a Tour finals spot on Friday when he made it through to the semi-finals of the Paris Masters with a 6-4, 6-7(5), 6-4 win over Argentine Juan Martin Del Potro as the tournament was hit by the withdrawal of Rafael Nadal.
Former world number one Rafa Nadal wasted a match point as he slipped to a surprise semi-final loss to Austrian Dominic Thiem on his beloved clay at the Argentina Open on Saturday.
The 32-year-old, who has not played since retiring injured in the US Open semi-finals, cited an abdominal injury.
With rain having washed out Wednesday's play, Federer along with champion Rafael Nadal and top seed Novak Djokovic all face playing back-to-back matches on Thursday if they want to reach the quarter-finals.
Andy Murray saved seven match-points in a 31-minute tiebreak that stretched to 38 points before he finally subdued Germany's Philipp Kohlschreiber 6-7(4), 7-6(18), 6-1 to reach the Dubai Championships semi-finals on Thursday.
IMAGES from matches on Day 8 at the French Open
The 33-year-old Swiss, ranked 261 in the world after two knee surgeries, served solidly throughout a one-sided contest on the slick centre court, easing past an opponent who struggled to cope with Wawrinka's power.
Although comprehensively beaten by Novak Djokovic on the Monte Carlo semi-finals, clay court king Rafael Nadal believes he is on the right path as his beloved French Open looms.
Rafa Nadal has returned to the Spain team as they seek to maintain their Davis Cup World Group status with a playoff tie against Ukraine in Madrid later this month, captain Alex Corretja said on Monday.
British Prime Minister David Cameron ignored growing speculation about the 'Curse of Cameron' on Wednesday by tweeting a message of support to Briton Andy Murray ahead of his quarter-final match at Wimbledon.
Defending champion Stan Wawrinka avoided a repeat on Wednesday of his first-round scare, though he was still made to work hard in a straight-sets win over Japan's Taro Daniel. The Swiss third seed won 7-6(7) 6-3 6-4 and is now on a six-match winning streak on clay, having warmed-up for Roland Garros by winning the title in Geneva last week. Progress was by no means straightforward against a skilful opponent ranked 93rd in the world and Wawrinka has yet to switch to his A game. But he says it's there when he needs it. "If you look at the first two matches, for sure I'm not playing my best tennis, but I know I have my best tennis in me," the 31-year-old Wawrinka, playing in his 45th consecutive grand slam tournament, told reporters.
It was the Russian's first competitive match since she withdrew from the St Petersburg Open in January.
Images from Day 4 of the Australian Open in Melbourne on Thursday
Defending champion Donna Vekic, of Croatia, earned a hard-fought win over British wild card Gabriella Taylor 7-5, 5-7, 7-6(3).
Top seed Agnieszka Radwanska's title defence at the Sydney International lasted just 92 minutes when she was dumped out of the second round by Bethanie Mattek-Sands on Tuesday.
Defending champion Novak Djokovic survived a scare.
Both won in style on Sunday, with Spanish fifth seed Nadal pouncing on Guido Pella's serve to break the Argentine five times en route to a 6-3, 6-2 victory in sizzling afternoon heat on the stadium hard court.
World number five Alexander Zverev continued his poor recent form as he crashed out of the Italian Open in the second round while Serena Williams had to pull out of the women's draw with a recurring knee injury.
Madison Keys beat fellow American CoCo Vandeweghe for the second time in eight days with a 6-4, 3-6, 6-3 victory on Monday to reach the second round of the Cincinnati Open.
Australia's Bernard Tomic thinks he is playing some of the best grasscourt tennis of his career and is in a good place off the court as he heads into the Wimbledon championships main draw for the seventh time.
Rafael Nadal's path to his Australian Open semi-final against Grigor Dimitrov on Friday has taught the 30-year-old Spaniard one thing -- he's still got it.
A deflated Novak Djokovic blamed a bad day at the office for his stunning second-round elimination by Uzbek wildcard Denis Istomin which condemned the Serb to his earliest grand slam exit in nearly a decade.
World number two Rafael Nadal dropped a set at the Barcelona Open for the first time in four years before advancing to the last 16, beating Argentine Leonardo Mayer 6-7(7), 6-4, 6-2 on Wednesday.
Novak Djokovic made an immense statement in his bid to rule men's tennis again when he defeated Andy Murray, the man who deposed him as world number one, 6-3, 5-7, 6-4 in an epic Qatar Open final in Doha on Saturday.
Rafael Nadal returns to his favourite tournament, albeit not his preferred court, to begin pursuit of a record-extending 10th French Open title on Monday against Frenchman Benoit Paire.
Will it be Rafa versus Djoko in Sunday's final?
India ended its campaign at the Fed Cup with a fourth place finish after losing the classification tie 1-2 to Korea as the team badly missed injured Karman Kaur Thandi, who did not play on Saturday, in Astana, Kazakhstan.
French Open champion Stanislas Wawrinka was scythed back to earth by big-serving South African Kevin Anderson on the Queen's Club grass as the Swiss bowed out of the Aegon Championships 7-6(4), 7-6(11) on Wednesday.
The franchise-based Champions Tennis League, which will begin its second season next month, will help end India's search for quality singles players, its promoter and former Davis Cupper Vijay Amritraj said.
Former World No 1 Ana Ivanovic was upset 7-5, 6-4 by 42nd-ranked Karolina Pliskova of the Czech Republic in the second round of the US Open on Thursday.
Novak Djokovic praised American Tim Smyczek's act of sportsmanship in his second round marathon against Rafa Nadal as "greater than sport itself" at the Australian Open on Thursday.
The seventh seeded pair beat the Austria-Brazilian combination of Alexander Peya and Bruno Soares 6-3, 5-7, 10-8 in an hour and 42 minutes.
IMAGES from the Miami Masters played in Key Biscayne, Florida on Tuesday
But for the 23-year-old Bouchard, a former world number five who has slumped to 56th in the rankings, it was another blow after her first-round exit in Indian Wells.
Top seeds Novak Djokovic and Serena Williams face challenging early tests at the US Open following Friday's draws for the year's last Grand Slam starting on Monday.
Serena faces hard-hitting Giorgi in first round while former World No Hewitt play his final grand slam
Check out some of the up-and-comers who could cause an upset at Wimbledon this year.