NEW YORK — For Serena Williams’ first 26 matches at major tournaments in 2015, no deficit was too daunting, no opponent too troublesome, no victory too far from reach.

She was unbeaten and, seemingly, unbeatable, nearing the first Grand Slam in more than a quarter-century. All Williams needed was two more wins to pull off that rare feat. And yet, against an unseeded and unheralded opponent in the U.S. Open semifinals, she faltered. Her pursuit of history ended, oh so close.

In one of the most significant upsets in the history of tennis, Williams finally found a hole too big to climb out of, losing 2-6, 6-4, 6-4 Friday at Flushing Meadows to 43rd-ranked Roberta Vinci of Italy.

“I don’t want to talk about how disappointed I am,” Williams said.

Vinci had never before played in a Grand Slam semifinal. She had never so much as taken a set off Williams, much less won, in four previous matchups.

But her style, full of slices and net rushes, kept Williams off-balance enough to cause problems and prevent the 33-year-old American from becoming the first player since Steffi Graf in 1988 to win all four Grand Slam tournaments in a single season. Williams had been pushed to the limit before — this was her 12th three-setter in a major this season — but had managed to win titles at the Australian Open on hard courts in January, the French Open on clay courts in June, and Wimbledon on grass courts in July.

This time, for once, the No. 1-ranked Williams could not pull it out, undone by 40 unforced errors, twice as many as Vinci. That negated the impact of Williams’ 16 aces, including one at 126 mph.

“I thought she played the best tennis in her career,” Williams said about Vinci. “She played, literally, out of her mind.”

Yes, remarkably, instead of Williams, it will be Vinci participating in Saturday’s final. She will face another Italian making her Grand Slam final debut: 26th-seeded Flavia Pennetta, who eliminated No. 2 Simona Halep 6-1, 6-3 earlier Friday.

Pennetta, 33, and Vinci, 32, have known each other since they were kids, having grown up in towns about 40 miles (65 kilometers) apart on opposite coasts of Puglia, a region in the southeastern heel of Italy’s boot-shaped peninsula.

Now they will face each other all these years later, halfway around the world, in a stadium in New York — with a Grand Slam trophy on the line. An intriguing story line and big stakes, to be sure, but nothing compared to what Williams was chasing: a perfect Grand Slam season.

After all, not only was she 26-0 at those tournaments this year, but her winning streak at majors actually was 33 matches entering Friday, because she won last year’s U.S. Open, too.

If she had managed to win a fifth consecutive major title, Williams would have raised her total to 22, equaling Graf for the most in the Open era, which began in 1968, and second-most in history behind Margaret Court’s 24.