The American, who will go down as an all-time great regardless of whether she does eventually equal Margaret Court’s record, was distraught after the defeat, breaking down in tears in her post-match press conference.
‘I had so many opportunities,’ she told reporters. ‘It was just … I made too many mistakes there and easy mistakes.’
Williams last claimed a Grand Slam title back in 2017, when she beat her sister Venus to claim the Australian Open, the 23rd major title of her prolific career.
She has now competed in 10 further Slams in a bid to match the record but fallen short on every occasion.
Having played such stunning tennis on the way to this year’s Australian Open semi-final – particularly in a straight-sets win over Simona Halep – this was another bitter blow to take.
And having reached four finals from those 10 attempts, Williams may now be wondering whether it will ever happen.
With that in mind, Sportsmail takes you back through Williams’ last 10 attempts at glory.
Serena Williams (39) was unable to match Naomi Osaka (23), who won 6-3 6-4 on Thursday
Osaka plays Jennifer Brady in Saturday’s final as she bids for successive Australian Open titles
Wimbledon 2018: Williams loses in the final
We start nearly three years ago in 2018, when Williams made her first attempt at a Grand Slam title since her victory in Australia the year prior.
Williams was perhaps fortunate with her route to the final, in which she played just one seeded player in Julia Goerges, who was ranked at 13th.
Nevertheless, the great champion made it to the final without any significant trouble, losing just one set – which came in her quarter-final against Camila Giorgi.
The final proved a step too far, however, as Angelique Kerber, who was seeded 10th, proved too strong with a 6-3 6-3 victory.
Just reaching the final was an extraordinary achievement for Williams, though, as she had given birth to her daughter just 10 months prior and played only four tournaments since.
Williams was understandably disappointed by the defeat, but gave a defiant message that more was to come.
‘It is obviously a disappointment but I can’t be disappointed,’ she said. ‘I’m literally getting started.
‘To the other mums out there I was playing for you today and I tried. But Angelique played really well. I look forward to continuing to be out there and do what I do best.’
US Open 2018: Williams loses to Osaka in the final
Serena Williams was furious with umpire Carlos Ramos throughout the 2018 US Open final
Just a few months later and Williams was in another final, this time against a 20-year-old Naomi Osaka, who won in straight sets to become the first-ever Japanese Grand Slam winner.
It was a match that truly announced Osaka to the world, though it was overshadowed by a series of arguments between Williams and the umpire.
Williams, who was 36 at the time, called the umpire both a ‘liar’ and a ‘thief’ throughout a match where she was docked a game for verbal abuse, given a point penalty for smashing her racquet and a code violation for an alleged breach of coaching rules.
The Flushing Meadows crowd were stunned when Osaka – who was 6-2 4-3 up at the time – was handed a game without hitting a ball after Williams called the umpire a ‘cheat’ during a barrage of insults.
Osaka went onto win the match 6-2 6-4 and was gracious in victory – just as Williams graciously congratulated her at the net.
Williams was later fined £13,100 for her court violations throughout, while in Osaka, a star was born.
Australian Open 2019: Williams loses in the last-eight
Serena Williams shouted in frustration as she lost to Karolina Pliskova in Australia
After finishing 2018 with a disappointing final defeat to Naomi Osaka, Williams continued her search for a 24th Grand Slam title at the Australian Open.
The American again came into the tournament as one of the favourites, which she certainly cemented with an impressive win over Simona Halep in the round of 16.
Halep was the top seeded player in the tournament, but Williams proved too strong for the Romanian, who was beaten 6-1 4-6 6-4.
Williams was drawn against seventh-seed Karoline Pliskova in the quarter-finals, where her tournament would come to a premature end.
It was another extraordinary defeat for Williams, who was 5-1 up in the third and final set before losing the match 6-4 4-6 5-7.
In fact, Williams lost four match points in the final set, and was even denied an ace at 5-1, 40-30 by a foot fault.
Williams appeared to turn her ankle following her second serve and was then broken and lost six games in a row on her way to defeat.
Who would she have faced in the next round you ask? Naomi Osaka.
French Open 2019: Williams loses in the round of 32
Sofia Kenin shocked the world with a 6-2 7-5 win over Serena Williams at the French Open
After failing to reach the semi-finals of the Australian Open by the tightest of margins, Williams was unable to reach the quarter-finals of the French Open a few months later.
The American started the tournament slowly, losing the opening set 6-2 against the unseeded Vitalia Diatchenko, though she bounced back well to progress.
However, Williams then came up against Sofia Kenin in round three, who ran out a comfortable 6-2 7-5 winner.
Though Kenin has, of course, since become a household name in the tennis world, the 20-year-old was certainly not expected to beat Williams then.
In fact, it was Williams’ earliest Slam exit for six years, when she was defeated by Alize Cornet at Wimbledon in 2013 at the same stage.
The defeat was a shock to many, but Williams had been suffering with a significant knee injury, which had prevented her from playing much tennis since the Australian Open.
In fact, Williams had not played more than two matches at any tournament since January’s major.
The wait for a 24th Grand Slam title went on.
Wimbledon 2019: Williams loses in the final… again!
Simona Halep became the first-ever Romanian to win at Wimbledon with victory over Williams
Williams had been struggling for form and fitness throughout 2019, but she found her mojo once more at Wimbledon.
The American had, of course, lost to Kerber in the final the year prior, but was out for redemption as she stormed her way to the final at SW19.
Williams fared no better this time, however, as Simona Halep dropped just four games in an astonishingly one-sided 6-2 6-2 win.
A packed Centre Court sat in dismay as Halep made just three unforced errors throughout the match… to Williams’ 26!
The match lasted just 56 minutes, with Williams subsequently stating Halep was just too good on the day.
‘She played out of her mind, it was a little bit deer in the headlights for me,’ she said.
For Williams, that was her third Grand Slam final defeat in just 12 months. Arguably the greatest player women’s tennis has ever seen just couldn’t quite get over the line for a 24th Slam.
US Open 2019: Another loss in the final for Williams
Williams’ wait for a 24th Grand Slam continued as Bianca Andreescu made history in New York
A few months later, Williams found herself in yet another Grand Slam final, with yet another chance to equal Margaret Court’s long-standing record.
Williams dropped just one set on her way to the final, reeling off wins against Maria Sharapova, Petra Martic, Qiang Wang and Elina Svitolina.
In Bianca Andreescu, Williams came up against another young and hungry competitor, who was playing in the main draw of the US Open for the very first time.
At just 19-years-old, the Canadian Andreescu shocked the Flushing Meadows crowd with a scintillating performance to take the match 6-3 7-5.
Despite all the experience in the world, Williams looked nervous throughout, even handing her opponent three of her five breaks of serve by way of a double fault.
Andreescu has gone on to remain one of the bright lights in the women’s game, currently sat at ninth in the world, aged just 20.
Australian Open 2020: Williams in shock early defeat
Williams looked dejected throughout her early defeat at the Australian Open last year
After reaching back-to-back Slam finals, an early exit came next for Williams, who was beaten by Qiang Wang in a highly competitive round of 32 encounter.
Williams came into the opening major of the calendar year on the back winning the Auckland Classic the week prior.
And after two straightforward opening rounds, Wang was not expected to be a problem in the third – particularly as Williams had just beaten her 6-1 6-0 in only 44 minutes at the US Open.
Williams put in a totally different performance this time round, however, throwing in an astonishing 56 unforced errors on the way to a 6-4 6-7 7-5 defeat.
Speaking after the match, Williams said: ‘I just made far too many errors to be a professional athlete today.
‘If we were just honest with ourselves, it’s all on my shoulders. I lost that match. It’s not about the tournament, it’s just like I can’t play like that.
‘I literally can’t do that again. That’s unprofessional. It’s not cool.’
US Open 2020: Williams falls just short again
Williams was beaten in three by a resurgent Victoria Azarenka despite taking the first set 6-1
Williams couldn’t hide her shock as she lost the next two sets to miss out on a place in the final
After reaching the final at the US Open in 2019, Williams returned to Flushing Meadows once more, still with the goal of winning a record-equaling 24th Grand Slam fresh in her mind.
The American, who came into the tournament seeded third, wasn’t her usual dominant self on her way to the semi-finals.
She came through her opening two rounds unscathed, but dropped sets in each of her next three matches.
Williams was prolific in her final-set deciders, however, beating Sloane Stephens, Maria Sakkari and Tsvetana Pironkova 6-2, 6-3 and 6-2 respectively.
Up next for Williams in the semi-finals was Victoria Azarenka, who was making an astonishing return to the elite of women’s tennis, having not reached a major final since 2013.
And though Williams took the first set 6-1, another final-set decider was needed as Azarenka levelled.
In the end, it was the Belarusian who prevailed, and Williams’ wait went on.
French Open 2020: Williams pulls out with injury
Williams withdrew after the first round at last year’s French Open due to an achilles injury
We are now almost at the present, with last year’s rearranged French Open the previous Slam Williams played in before the current Australian Open.
Williams elected to enter the tournament despite struggling with an achilles injury suffered in her US Open defeat to Victoria Azarenka.
The veteran was fit enough to brush aside her fellow American Kristie Ahn in the first round, but she subsequently revealed she had been struggling throughout.
Williams was scheduled to face Tsvetana Pironkova in the second round, but she was unable to recover and was forced to withdraw.
And that takes us up to today, where Williams’ Australian Open hopes were dashed by the reigning champion Naomi Osaka.
Will it ever happen for Williams?
Analysing Williams’ last 10 attempts to finally equal Margaret Court’s long-standing record, two things are apparent.
Primarily, there are some seriously talented players that have emerged in recent years, none more so than Sofia Kenin, Bianca Adreescu and, most prominently, Naomi Osaka.
Having been beaten by a 20-year-old Osaka in the final of the US Open in 2018, and by a 19-year-old Andreescu again at Flushing Meadows a year later, it does feel as if a new generation is in town.
And at 39-years-old, Williams simply just isn’t the force she used to be, with injuries starting to pile up as well.
One thing you can never do is rule out Serena Williams, however. And perhaps this prolonged wait to equal Court’s record will only make it sweeter if she does.
Regardless, whether Williams does go onto equal the record or not, she is arguably the best-ever player to ever compete in the women’s game.