The Slovakian eventually won 6-4, 6-1 but the match will be remembered for a ludicrous umpiring decision at a crucial stage of a tight opening set.
Maria Sharapova is renowned for her sheer determination in the face of adversity but in Singapore on Saturday, the Russian was quick to cast doubt over her chances of winning the WTA Finals after an injury-ravaged second half of the season.
Japan's Kei Nishikori and Victoria Azarenka of Belarus continued their Australian Open preparations by swiftly marching through to the quarter finals of the Brisbane International on Wednesday.
A six-time champion at Flushing Meadows, Williams was once money in the bank when it came to the US Open
Roger Federer is keeping a lid on expectations.
Serena William powered her way to within two victories of a seventh US Open title on Tuesday and while she refused to look ahead there are many willing to do it for her, and what they see is a suddenly open path to a 24th Grand Slam.
'The toughest is what's to come. I hope that I'll be able to take that and play even better'
The Australian Open will lose one of its giant killers when South Korean Chung Hyeon meets American Tennys Sandgren in an unlikely quarter-final showdown at the Rod Laver Arena on Wednesday.
The sixth seed burnt the midnight oil in her all-Czech fourth round grudge match against Barbara Strycova, finally clinching a 6-7, 6-3, 6-2 victory at 1.35 a.m. local time on Tuesday morning.
Roger Federer gained a measure of revenge against Wimbledon nemesis Kevin Anderson, beating the South African 6-0, 6-4 at the Miami Open on Thursday to set up a mouthwatering semi-final against a player barely half his age.
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.
Images from Day 9 at the French Open.
Champions were dethroned, new national heroes born and world records smashed
Third seed Stan Wawrinka was sent packing in the round of 16 at the BNP Paribas Open in California on Wednesday and was very nearly joined by Rafael Nadal, who pulled off a Houdini-like escape to reach the last eight.
Spaniard Garbine Muguruza withdraw from the Italian Open semi-finals with a neck injury on Saturday, eight days before she is due to start the defence of her French Open title at Roland Garros.
The Canadian's win sets up a semi-final clash with Del Potro on Saturday that will pit power against power.
Former world number one Victoria Azarenka was forced out of the Aegon Classic in Birmingham with a foot injury on Wednesday shortly after defending champion Ana Ivanovic suffered a shock defeat.
Now with Serena sidelined for the impending birth of her first child, the two-time grand slam winner is delivering on the promise that could see her become the new face of women's tennis.
Osaka survives test to reach last 16
Serena Williams shook off the rust and a feisty challenge from Serbia's Ana Ivanovic to open the defence of her WTA Finals title with a 6-4, 6-4 victory in the opening match of the elite eight-player tournament on Monday.
The 36-year-old has been practising hard on the grass and few would bet against her becoming the first mother to win the title since Evonne Cawley 38 years ago.
The 36-year-old Swiss master needs only to reach the semi-finals at the ABN Amro tennis event to overtake Rafael Nadal at the top of the ATP rankings and become world number one for the first time since November 2012.
A calm Sloane Stephens picked her shots to perfection to overcome Japan's Naomi Osaka in a battle between the last two US Open champions at the WTA Finals on Monday before top seed Angelique Kerber was upset by Kiki Bertens.
Petra Kvitova takes on Naomi Osaka in Saturday's Australian Open final with one of them set to emerge as a fresh champion at Melbourne Park as well as the new world number one.
List of Australian Open women's singles champions since the event began in 1922 (Australian unless stated):
Serena Williams rallied to avoid a stunning upset and secure a 1-6, 6-3, 6-3 semi-final win over Czech qualifier Marie Bouzkova at the Rogers Cup on Saturday, setting up a title showdown with local teenager Bianca Andreescu.
Former men's champion Mats Wilander believes third seed Muguruza now looks like the most likely champion, having not dropped a set and thrashing Maria Sharapova on Wednesday.
Zhang Shuai stunned Wimbledon Champion Angelique Kerber 6-1, 2-6, 6-0 in the China Open on Thursday to set up a quarter-final clash with Naomi Osaka.
The draw for the first Grand Slam of the season was made on Thursday and the top seeds could face some early tests of their credentials when play gets underway in Melbourne on Monday.
Summary of sports events and persons who made news on Wednesday
Sam Stosur powered into the French Open quarter-finals with a 7-6(0), 6-3 win against Simona Halep in Paris on Tuesday, adapting better to damp and heavy conditions than her higher-ranked Romanian opponent.
Images from Tuesday's matches at the Australian Open.
Former world number one Garbine Muguruza was beaten 7-5, 6-4 by Aryna Sabalenka in the China Open second round on Tuesday while an ailing Jelena Ostapenko lost 6-0, 6-0 to Wang Qiang.
'Maria will look at it and see no one dominant. Serena Williams is the only player in the past who has been like a thorn in her side, but she feels mentally superior to most of the other and she feels she can win against them all'
Images from the second day's play of the 2016 French Open at the Roland Garros
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Maria Sharapova was dogged by injury and controversy as she tried to get her career back on track.
Czech defending champion Katerina Siniakova fended off Maria Sharapova in a fiercely contested match at the Shenzhen Open on Friday to set up a final with world number one Simona Halep.
Serena Williams recovered from a set down to beat Australian Ashleigh Barty 3-6, 6-3, 6-4 and book a place in the third round.
Images from Day 2 of the Australian Open in Melbourne on Tuesday