The Spaniard is odds-on favorite to win a 19th Grand Slam title after Novak Djokovic and Roger Federer were both knocked out.
Federer chases a first semifinal at Flushing Meadows since 2015, while Williams looks to take another step towards a 24th Grand Slam title.
Federer takes on Britain's Dan Evans, while Djokovic faces American qualifier Denis Kudla on Friday evening.
Coco Gauff plays Hungary's Timea Babos, while Rafael Nadal takes on Australia's Thanasi Kokkinakis on Thursday.
The world No. 1 and the world No. 3 are both in action on Wednesday, as are the Williams sisters.
Rafael Nadal and Coco Gauff are both in action on Tuesday as the first round of the U.S. Open is completed.
The world number one takes on the number 23 seed as he looks for a second consecutive Wimbledon final.
Federer and Nadal will renew their rivalry on Centre Court on Friday, 11 years after they last met in an epic final.
Roger Federer and Rafael Nadal go head-to-head at Wimbledon for the first time in 11 years on Friday.
Men's tennis's Big Three have looked in imperious form so far and are all in action in the quarterfinals at Wimbledon on Wednesday.
Federer plays Italy's Matteo Berrettini, Nadal takes on Portugal's Joao Sousa and Djokovic faces France's Ugo Humbert.
Federer plays Britain's Jay Clarke in the second round, while Nadal takes on Nick Kyrgios in a potentially tricky encounter.
Roger Federer, Rafael Nadal and Serena Williams begin their campaign at Wimbledon on Tuesday morning.
The 133rd edition of the oldest Grand Slam tournament begins on Monday as Federer looks for a ninth Wimbledon crown.
The 133rd edition of the oldest Grand Slam tournament gets underway on Monday as Novak Djokovic and Angelique Kerber look to defend their titles.
The semifinals of both the men's and the women's tournament are scheduled for Friday, June 7 as Rafael Nadal and Roger Federer go head-to-head again.
The two rivals go head-to-head in the French Open semifinal on Friday and experts believe Nadal will have the better of his old foe again.
The world number two and number three are in action on Tuesday and could meet in the semifinal
Roger Federer aims to clinch a ninth Wimbledon crown while Serena Williams returns to action.
From soccer to tennis to basketball, it's clear that it pays to be gifted athletically.
The Swiss maestro, appearing in his 11th Wimbledon final, was challenged early on but once he broke a nervous Cilic in the fifth game of the opening set the match became a no-contest.
Age and experience have been key this year in SW19.
Research shows top players grunted at a higher pitch in matches they lost.
The big four have dominated the men's singles game at SW19.
Murray begins his defense on Monday in London.
The Swiss wants to concentrate on the grass-court season.
Four all-time tennis greats will clash this weekend in the Australian Open finals.
They last met in a Grand Slam final in 2011.