The top-seeded Serb, who had not dropped a set in four matches since the round of 16 at the Australian Open in January, looked out-of-sorts throughout the 98-minute contest.
World No 1s Andy Murray and Angelique Kerber have been named top seeds for the first major of the season, Australian Open, which will commences on January 16.
Big-serving Canadian Milos Raonic fired 19 aces to topple Sam Querrey 6-4, 6-4 and set up a second-round clash with either Dan Evans or Russian 10th seed Andrey Rublev.
Japan's Naomi Osaka claimed her first career title with a commanding 6-3, 6-2 victory over Russian Daria Kasatkina in a battle of 20-year-olds at the BNP Paribas Open on Sunday.
Russian President Vladimir Putin said on Friday World Anti-Doping Agency (WADA) records leaked by hackers raised a lot of questions with healthy athletes seemingly taking banned substances, TASS news agency reported.
The World Anti-Doping Agency (WADA) said on Wednesday that another batch of athlete data has been leaked by the same Russian cyber espionage group that published confidential data earlier this week.
Karolina Pliskova suffered a narrow US Open defeat at the hands of Angelique Kerber on Saturday, but the Czech 10th seed also proved her mettle as one of the most dangerous attacking players in women's tennis.
Wimbledon champion Garbine Muguruza notched up her first ever victory on Arthur Ashe Stadium with a 6-0, 6-3 win over American Varvara Lepchenko at the US Open on Monday.
Late-blooming Johanna Konta won the biggest title of her career when she beat Caroline Wozniacki 6-4, 6-3 in the women's final at the Miami Open on Saturday.
The top women's seeds continued to be scattered at Wimbledon on Wednesday, with Caroline Wozniacki's exit meaning five of the top eight were gone before the end of the third day.
Form guide for American Serena Williams ahead of Thursday's US Open semi-final clash against Latvia's Anastasija Sevastova:
The absence of Japan's Kei Nishikori from this year's Australian Open has turned the spotlight on Chung Hyeon as Asia waits for its first men's Grand Slam singles champion.
Reigning French Open champion Maria Sharapova, former world number one Venus Williams and Australian Samantha Stosur sailed into the second round of the China Open with straight set victories on Sunday.
India's Leander Paes and his German partner Alexander Zverev went down to the Spanish duo of Feliciano Lopez and Marc Lopez in a men's doubles first round match to bow out of the Cincinnati Open.
Bertens, the first Dutchwoman to reach the last 16 since Michaella Krajicek, sister of former men's champion Richard, did so in 2007, followed up her win over Venus Williams in the third round with a display of power and poise.
Rediff.com takes a look at some interesting highlights of the tournament.
The signs that things were going horribly wrong for Roger Federer were laid bare at Roland Garros.
Tennis player Prarthana Thombare, who will partner India ace Sania Mirza in the Olympics, says she is not scared of facing the big names at Rio Games as she has the World No. 1 beside her.
Images from Day 1 of the Australian Open in Melbourne on Monday.
Documents relating to Farah, and published on the fancybear.net website, showed that the distance runner had no active Therapeutic Use Exemptions (TUEs) at the time of the Olympics. TUEs allow athletes to take banned substances for verified medical needs and there is no suggestion any of those named have broken any rules
Rafael Nadal won a record 34th ATP Masters 1000 title with a 6-0, 4-6, 6-1 victory over Novak Djokovic in the Italian Open final on Sunday.
Novak Djokovic, Rafael Nadal and Johanna Konta progressed to the Italian Open semi-finals on Friday, but Roger Federer and Naomi Osaka were forced to withdraw with injury problems. World number one Osaka pulled out of her quarter-final meeting with Kiki Bertens due to a thumb injury before 37-year-old Federer announced his withdrawal because of a problem to his right leg.
Serena Williams beat crowd favourite Kim Clijsters in one of the greatest comebacks in tennis history.
It was a day of surprises at Flushing Meadows in New York as seeded players were knocked out one after the other on Friday.
Maria Sharapova's contentious and captivating US Open run came to an end on Sunday when Latvia's Anastasija Sevastova beat her 5-7, 6-4, 6-2 to reach the Flushing Meadows quarter-finals.
Serena Williams said on Saturday the COVID-19 outbreak has not only given her a much needed stretch of downtime with her family, it has also turned her into a bit of a "neurotic" and "a recluse" given her past health scares.
The 17th seed has been in no-nonsense mood so far in Melbourne, moving through the rounds with the minimum of fanfare, but faces her biggest test against the German.
Johanna Konta's exhilarating run at the Australian Open was finally halted by Angelique Kerber in the semi-finals on Thursday, but the Briton leaves Melbourne Park 'hungry' for more Grand Slam success.
Thursday's match was just Venus Williams's seventh of the year and first since January's Australian Open, where she fell to Simona Halep in the round of 32.
Canadian teenager Bianca Andreescu's Indian Wells triumph was not shown on television in her home country but that did not dampen the excitement across a nation where the future of women's tennis is suddenly looking as bright as ever.
World number one Serena Williams slammed Shamil Tarpishchev for using "extremely sexist, racist and bullying" comments after the Russian Tennis Federation (RTF) president described her and sister Venus as the "Williams brothers".
Serena will not be in the US team for the Tokyo Olympics
Being the reigning Wimbledon champion and former French Open winner has its perks for Garbine Muguruza, like being invited to walk the red carpet at this year's Oscars in Hollywood.
Tennis World No 5 Rafael Nadal and Olympic champion Mo Farah have spoken in defence after Russian cyber espionage group Fancy Bears leaked their medical data on Monday.
Photos from the Wimbledon matches on Day 1
Factbox on Wimbledon champion Marion Bartoli, who announced her retirement from tennis at 28 after a second round loss at the Western and Southern Open in Cincinnati on Wednesday.
The 'Big Four' of men's tennis have made it into the second week of Wimbledon unscathed and largely untroubled while the women's draw remains wide open, but "Manic Monday" could offer major clues as to the destination of this year's titles.
Triple Tour de France champion Chris Froome says he has "no issue" with his private medical records being leaked in a cyber attack by Russian hackers on the World Anti-Doping Agency (WADA).
French Open organisers, having been criticised for allegedly ensuring the players stayed on court in the rain, came under fire for sending them back to the dressing room on Thursday.
Rafael Nadal knows only too well what it's like to miss out on playing at the Olympics, hence he does not understand why so many of his fellow tennis professionals are turning their backs on the Rio Games in August.