Less than a month after her run to the Wimbledon final, where she lost to Spain's Garbine Muguruza, 37-year-old Williams again had to turn back time against a young challenger.
Here is a timeline of Djokovic's decline since the last of his 12 Grand Slam titles.
A relentless Novak Djokovic shrugged off Juan Martin Del Potro while Andy Murray overcame a nasty ankle injury as the second and fourth seeds joined champion Rafa Nadal in the French Open fourth round on Saturday.
Rafa Nadal thrashed Juan Monaco and David Ferrer rallied to fell Juan Martin Del Potro in five thrilling sets to give Spain a 2-0 lead over Argentina in the Davis Cup final on Friday that put the favourites on the brink of a fifth title.
Fifth seed Andy Murray, sixth-seeded David Ferrer and defending champion Ivan Ljubicic all fell by the wayside on a day of startling upsets at the Indian Wells ATP tournament on Saturday.
Marin Cilic overcame Federico Delbonis 6-3, 7-5, 3-6, 1-6, 6-2 after a titanic tussle in the opening singles rubber to give hosts Croatia a 1-0 lead over Argentina in the Davis Cup final on Friday.
World number two Novak Djokovic expects Stanislas Wawrinka and Andy Murray to lift their game at the French Open despite failing to make an impact so far in the clay court season.
Order of play on the main show courts at the French Open.
'He's one of those players that are dangerous for everybody'
An elbow injury forced Djokovic to retire against Czech Tomas Berdych in the quarter-finals of Wimbledon in 2017. After that came a series of early tournament exits and, finally, surgery.
The 32-year-old debutant at the ATP's blue riband event won the first 11 games of the round-robin clash before a relieved Nishikori finally got on the scoreboard with an angled winner.
Here are images from a hot, hot day from Melbourne Park...
Rafael Nadal gave Russian teenager Andrey Rublev a tennis lesson on Wednesday, racing into the semi-finals of the US Open with a ruthless 6-1, 6-2, 6-2 win that cleared the path for a possible showdown with rival Roger Federer.
Rafael Nadal swept into the quarter-finals of the Italian Open on Thursday with a ruthless 6-4, 6-1 victory over Canadian teenager Denis Shapovalov. The top seed, who will reclaim the world number one ranking from Roger Federer if he wins his eighth title in Rome, turned in a near-flawless performance, losing only five service points as he honed in on victory in an hour and 22 minutes.
Images from day one of the US Open tennis championships in New York, on Monday.
All of a sudden, talk of Roger Federer's supposed decline has disappeared and he is looming as the form player heading into the U.S. Open brimful of confidence.
Novak Djokovic endured a fierce challenge to his Melbourne Park reign before overhauling Dominic Thiem 6-4, 4-6, 2-6, 6-3, 6-4 on Sunday to clinch an eighth Australian Open crown and reclaim the world number one ranking. While Rafa Nadal rules Roland Garros with 12 titles, Djokovic holds sway in the title match at Rod Laver Arena having never lost a final in Melbourne Park.
Somdev Devvarman frittered away chances galore and crashed out of the men's singles at the Dubai Duty Free Championships after a straight sets defeat to fellow-wild card Malek Jaziri in the second round on Wednesday.
World number one Rafael Nadal was installed as the top men's seed for the US Open on Monday as the Spaniard bids to complete a career grand slam.
List of US Open men's singles champions since tennis turned professional in 1968.
Roger Federer is looking forward to facing his great rival for the French Open crown a year after Rafael Nadal missed their rendezvous in the final. With usual contenders Nikolay Davydenko of Russia and Argentine Juan Martin Del Potro having pulled out injured, the road looks clearer for another Roger versus Rafa classic.
Raucous home support for holders Argentina did not make up for the absence of Juan Martin del Potro and Federico Delbonis on Friday as they fell 2-0 behind to Italy in the first round of the Davis Cup.
Novak Djokovic sat out last year's U.S. Open to rest an elbow injury that eventually required surgery, but that pain and frustration felt like a distant memory on Friday when the Serb completed his march to the New York final with authority.
The Scotsman doesn't expect to win US Open this year
Russia's Nikolay Davydenko hopes his dazzling displays to win the ATP World Tour Finals title will finally allow him to step out of the shadow of compatriot Marat Safin who retired this month.
Marat Safin, widely regarded as one of the most gifted players of his generation, brought down the curtain on a chequered career when he bowed out to US Open champion Juan Martin del Potro in the Paris Masters.
Marin Cilic hit all the right notes in a dominant 6-3, 6-3, 6-3 win over Kei Nishikori in the US Open final on Monday but it remains to be seen if the big Croatian is another one Slam wonder or perennial threat.
World number one Roger Federer missed out on a fourth successive Swiss Indoors title when he lost to third-ranked Novak Djokovic in the final of his hometown tournament on Sunday. The Serbian won 6-4, 4-6, 6-2 to record his third win over Federer in five meetings this year.
Jurgen Melzer upset top seed Marin Cilic 6-4, 6-3 in the final of the Vienna Open on Sunday to become the first home player to win the tournament for 21 years.
Top seed Marin Cilic stayed on course for a third ATP title this year with a comfortable victory over Spain's Feliciano Lopez in their Vienna Open quarter-final on Friday.
American Andy Roddick has booked his place at the World Tour Finals with four weeks of the season remaining, the ATP said on Tuesday.
World number two Rafael Nadal has pulled out of next week's Thailand Open because of an abdominal injury, organisers said on Monday. The Spaniard was due to visit the Kingdom this week for a beach holiday ahead of the $608,500 tournament in Bangkok. He will stay in Spain to receive treatment for what his doctor said is an acute rupture of an abdominal muscle.
Roger Federer sought consolation in a golden summer rather than dwelling on defeat after his upset loss to Juan Martin del Potro in the US Open final.
Briton Andy Murray overcame sweltering heat to beat Argentine Juan Martin del Potro 6-7, 7-6, 6-1 in the Montreal Masters final on Sunday. A day after replacing Rafael Nadal as world number two, Murray delivered a gritty performance to wear down the towering Argentine in two hours, 42 minutes.
World number two Simona Halep beat Maria Sharapova 6-2, 6-2 in the China Open third round on Wednesday for her first win over the Russian in eight attempts.
World number one Rafael Nadal set a new record of winning 50 consecutive sets on a single surface by beating Argentine Diego Schwartzman 6-3, 6-4 on Thursday to reach the Madrid Open quarter-finals.
Making women play best of five-set matches at the grand slams would be a waste of time because they are not fit enough to last the distance, former Wimbledon champion Lleyton Hewitt said on Tuesday.
Top seed Rafael Nadal overcame fellow Spaniard Fernando Verdasco 6-3, 6-3 at the Rome Masters on Friday while Roger Federer beat German qualifier Mischa Zverev 7-6, 6-2 to book a semi-final with holder Novak Djokovic. Serb Djokovic eased through with a 6-3, 6-4 triumph over Argentine fifth seed Juan Martin Del Potro. Nadal next faces Chilean 12th seed Fernando Gonzalez, a 2-6, 6-3, 6-4 winner over Argentine qualifier Juan Monaco.
World number two Roger Federer fended off a feisty challenge from German qualifier Mischa Zverev on Friday to win 7-6, 6-2 and set up a semi-final against defending champion Novak Djokovic. Serbian Djokovic eased confidently into the last four with a 6-3, 6-4 win over Argentine fifth seed Juan Martin Del Potro.
Novak Djokovic, Andy Murray, Rafael Nadal and Roger Federer all picked up third round wins at the Western and Southern Open on Thursday to set up a star-studded last eight in Cincinnati.