|2019 US Open|
|Venue: Flushing Meadows, New York Dates: 26 August-8 September|
|Coverage: Live text and radio commentary on selected matches on the BBC Sport website and app|
The Scot, who had hip surgery in January, had planned to play doubles but is focusing on singles elsewhere.
In his absence, the country’s number ones Johanna Konta and Kyle Edmund will carry British hopes in New York.
Swiss great Federer, 38, is seeking a record sixth men’s US Open singles title that would also make him the oldest men’s Grand Slam singles champion in the Open era.
Meanwhile, 37-year-old American Williams – whose defeat by Osaka in last year’s final was marred by her angry outbursts at the umpire – is hoping to equal the all-time record of 24 Grand Slam singles titles.
The tournament at Flushing Meadows, where singles winners take home $3,850,000 (£3.17m), features day and night sessions (16:00 BST and 00:00 BST) for most of the rounds.
- Williams faces Sharapova in US Open first round
- Federer feels ‘best in years’ for US Open
- Live scores, schedule and results
Konta and Edmund lead British hopes
At 16th in the world, Konta is the highest ranked Briton in the singles at Flushing Meadows and the 28-year-old will be seeking to translate her excellent form from earlier in the year into success here.
But the French Open semi-finalist, who also reached the last eight at Wimbledon, has had back-to-back first-round exits in her warm-up events. She plays Russia’s Daria Kasatkina at 16:00 on Monday.
Konta was the only British woman to have direct entry to the main draw, with Harriet Dart making it through qualifying to face Romanian Ana Bogdan, also at 16:00 on Monday.
British men’s number one Edmund, whose best result at the US Open was reaching the fourth round in 2016, is joined by Dan Evans and Cameron Norrie.
Edmund will open his campaign on Tuesday against Spaniard Pablo Andujar while Evans and Norrie both face Frenchmen on court 10 on Monday. Evans plays Adrian Mannarino before Norrie takes on Gregoire Barrere.
Jamie Murray will be among the Britons in the doubles, with the six-time Grand Slam champion seeking a maiden title with new partner and compatriot Neal Skupski.
Murray’s brother Andy will be playing at a Challenger event in Mallorca – the Rafa Nadal Open – from Monday as he steps up his recovery from career-saving hip surgery with more singles matches.
Williams has chance of redemption and record
Last year’s women’s final will be remembered for Williams’ outbursts, where she called umpire Carlos Ramos a “thief” and “liar” after he docked her a game before later accusing him of “sexism”.
Organisers are ensuring the pair will not cross paths this year, with Ramos not officiating any matches featuring Williams or her sister Venus.
Although Williams congratulated Osaka at the net at the end of the match and also later apologised to her, the events overshadowed the 21-year-old becoming the first Japanese to win a Grand Slam and left her in tears.
There are question marks over the fitness of Williams, who has retired or withdrawn from all five of her non-Grand Slam events this year.
The American, who is seeking to equal Margaret Court’s record of 24 Grand Slam singles titles, missed this month’s Cincinnati Masters with the back problem that forced her to pull out of the Rogers Cup final a few days earlier.
She faces a blockbuster first-round match against Russian five-time Grand Slam champion and long-time rival Maria Sharapova, which opens day one’s night session on Arthur Ashe Stadium. Sharapova has played just six matches since January because of a shoulder injury.
Since returning to tennis after giving birth in September 2017, Williams has reached three Grand Slam finals but has lost in all of them, including July’s Wimbledon defeat by Simona Halep.
Can Osaka handle the pressure?
After sealing her maiden Grand Slam last September, Osaka followed it up with an Australian Open victory that propelled her to the top of the world rankings.
But since then she has struggled with injury, poor form and says she “hasn’t enjoyed” tennis since that Melbourne triumph in January.
After her surprise third-round exit from the French Open in June, she said it was “probably the best thing that could have happened” and that she was suffering headaches from the “stress” of being the top seed.
Since then she briefly lost the world number one ranking to Australia’s Ashleigh Barty but has now regained it and, assuming she shakes off a recent knee injury, will once again need to prove she can handle the pressure of being the player to beat.
Among those seeking to capitalise if she falters will be world number three Karolina Pliskova, who, like Barty, could oust Osaka from the top with a good run.
The Czech 27-year-old, runner-up in 2016, has won three WTA titles this year and reached the semi-finals of the Cincinnati Masters.
Wimbledon champion Halep will be chasing a third Grand Slam title although her preparations have been hampered by an Achilles problem, while Cincinnati champion Madison Keys arrives at her home Grand Slam in good form as she seeks to improve on her runner-up finish from 2017.
Will Gauff build on Wimbledon run?
Two months after charming Wimbledon, American 15-year-old Coco Gauff will be aiming to build on that stunning run to the last 16 that included a first-round victory over seven-time Grand Slam singles champion Venus Williams.
In June she became the youngest player in the Open era to qualify for the main draw at Wimbledon and her exploits earned her a wildcard into the main draw at Flushing Meadows.
Victory alongside 17-year-old Catherine McNally in the Washington Open doubles final this month can give Gauff extra confidence before her US Open campaign, where she faces Russian world number 76 Anastasia Potapova in the first round.
Djokovic favourite to defend title
World number one Djokovic is the overwhelming favourite to defend his title and win a 17th Grand Slam crown, which would leave him just one behind Rafael Nadal and three behind leader Federer on the all-time list of men’s champions.
The 32-year-old Serb has won four of the past five Grand Slams and, after reaching the Cincinnati semi-finals, said: “I like my chances [at the US Open]. I feel good. I love playing in those conditions there on centre court.”
He will hope that conditions are less humid than last year when a series of players were forced to retire in the opening days because of heat-related issues and Djokovic himself said he had “struggled”.
The big three of Federer, Nadal and Djokovic have won the past 11 Grand Slam titles and it is hard to see beyond them once again at Flushing Meadows.
Time is, however, increasingly against Federer. The Swiss great turned 38 earlier this month and the most recent of his five US Open titles was 11 years ago. He was also surprisingly beaten in straight sets by 21-year-old Russian qualifier Andrey Rublev in the third round at Cincinnati this month.
But having held two championship points against Djokovic at Wimbledon just six weeks ago, he may feel he has some unfinished Grand Slam business.
“The way I played at Wimbledon is going to give me some extra confidence,” Federer said. “This is probably the best I’ve felt in years coming into the US Open, which is encouraging.”
Nadal, meanwhile, has warmed up by defending his Rogers Cup title – the first time he has retained a non-clay title.
The key for the 33-year-old Spanish world number two will be staying fit, having retired from his semi-final in New York a year ago with a knee problem that has caused him problems throughout his career. He withdrew from Cincinnati two weeks ago because of fatigue.
Last year’s runner-up Juan Martin del Potro is absent, having re-fractured his kneecap during Queen’s in June.
Who can challenge the ‘big three’?
It is the question that is posed before every Grand Slam and the one the next generation have so far been unable to answer with any conviction.
Germany’s Alexander Zverev and Greek Stefanos Tsitsipas are among the players in their early twenties who are in the top 10 but have lost momentum in their bid to challenge the ‘big three’.
Since beating Djokovic to win the prestigious ATP Finals last November, Zverev has reached just one Grand Slam quarter-final, while Tsitsipas followed up his Australian Open semi-final in January with a first-round exit at Wimbledon.
Russian 23-year-old Daniil Medvedev, who has risen to a career-high number five in the world rankings after his Cincinnati triumph, is the in-form player having reached three successive finals this month and could be one to watch.
Meanwhile, the spotlight will also be on Australian 24-year-old Nick Kyrgios, who oscillates between the talent that won him the Washington title this month and the behaviour that cost him $113,000 (£93,254) in fines less than a fortnight later.