Serena Williams has long since ensured she will go down as one of the tennis greats, but Friday's astonishing US Open defeat to Roberta Vinci could rankle the world number one for the rest of her days.

The legendary American has won 21 grand slam titles in her stellar career and is arguably the best female tennis player ever to play the game.

When Williams won Wimbledon in July it appeared there was no stopping her as she stood on the brink of winning a first calendar Grand Slam.

With the Australian and French Open titles already in the bag, the 33-year-old headed for her home slam in New York as a huge favourite to complete a clean sweep of major titles in 2015.

Williams had refused to entertain questions over her quest to become the first player since Steffi Graf in 1988 to win a calendar Grand Slam, but after her triumph on the grass at the All England Club it seemed she realised it was within her grasp.

Having been crowned champion three years in a row at Flushing Meadows - and six times in total - it was difficult to envisage the sporting icon being denied in New York.

But Vinci had not read the script, as she pulled off one of the most jaw-dropping upsets of all time to stun the top seed and ensure history will not be made by Williams on Saturday.

The unseeded Italian battled back to win 2-6 6-4 6-4 and stun an expectant crowd at Arthur Ashe Stadium on Friday to reach her first grand slam final. 

World number 43 Vinci had not been beyond the quarter-finals at a major before her unexpected exploits this week.

She had lost her previous four encounters with Williams before their semi-final encounter, so it seemed the outsider had little chance of pulling off the most famous victory of her career.

But as an out-of-sorts Williams appeared to freeze with so much at stake, racking up as many as 40 unforced errors in an uncharacteristically nervy display, it was Vinci who rose to the occasion.

The thousands who scrambled for tickets expecting to see Williams celebrate on home soil will instead face the prospect of watching an all-Italian final between Vinci and another surprise package in the form of Flavia Pennetta.

A downbeat Williams appeared to be startled as she stormed off the court and was crestfallen in her post-match news conference as she refused to put her disappointment into words.

Williams insisted nerves were not to blame for her defeat, but whatever the explanation is for such a below-par performance, she must now reflect on what might have been. 

While Williams will surely add to her tally of 21 grand slam titles to move level with Graf, she may never come so close to winning a calendar Grand Slam.