Murray had been given the toughest of first-round draws against last year’s beaten semi-finalist at Melbourne Park.
But at a venue where tennis had seemingly bid farewell to him four years ago, the 35-year-old had promised a long run having claimed to have worked harder than ever before over the course of the winter.
And for nearly five hours, his previously frail body did not let him down, while his mental fortitude was no less impressive to save a match point when serving at 4-5 down in the final set.
But he saved it when Berrettini limply hit a backhand into the bottom of the net and then Murray won the subsequent super tiebreak for a 6-3, 6-3, 4-6, 6-7, 7-6 victory.
Berrettini had no answer to Murray’s game plan in the opening two sets. On 158 times in his illustrious career, the Briton had won when winning the opening two sets, the only blemish a 2005 Wimbledon loss to David Nalbandian in the infancy of his career.
Eighteen years on at the age of 35, Murray rolled back the years to produce his best performance since undergoing hip surgery for what was his 50th Australian Open win. He will face either Thanasi Kokkinakis or Fabio Fognini in the second round.
Five times Murray has made the final in Melbourne without lifting the title aloft. Suddenly another long run doesn’t seem so far fetched if his body can recover from the toils of the sort of marathon match that has become a feature of his career.
Afterwards, an emotional Murray said: “I’ll be feeling this this evening and tomorrow. I’m unbelievably happy and proud of myself. I put a lot of work into the last few months with my team to give me the opportunity to perform on stadiums like this… against players like Matteo and it paid off tonight.
“That’s the first time I’ve ever played one of those 10 point tiebreakers. He came back really strong and I was a bit lucky at the end. Some of the tennis at the end was really good. He was serving unbelievable and he’s a brilliant competitor. He always fights right to the end. I did well to get through.”
Australian Open 2023 - In pictures
Murray’s apparent exit from tennis at the same stage of the Australian Open in 2019 to Roberto Bautista Agut had also gone to five sets, and this contest looked set for a similarly painful conclusion as Berrettini turned the tide.
The Italian’s serve and forehand looked impenetrable while Murray appeared on occasions a little heavy legged in the final set. Berrettini will be left to rue what might have been, with a very winnable backhand to break his rival and win the match but it went horribly wrong.
Tennis is so often about small margins and so it proved. From that point, Murray continued to pepper Berrettini’s weaker backhand and it was regularly found wanting.
A match that will live long in the memory could well have been finished off much earlier had Murray taken one of two break points to go 2-1 up in the third set. But he failed to do so and was broken in the very next game.
Using all his fight, though, he maintained his remarkable career record when leading by two sets for his first victory over a top-20 opponent at a Grand Slam since the 2017 French Open.
The record books may have been in Berrettini’s favour - he had won his last nine tiebreaks at the Australian Open - but Murray never looked back from taking an early break in that super tiebreak.
The last point was not quite befitting of what had been a breathtaking contest, his final shot hitting the net and limping its way over Berrettini’s side of the court for the biggest win of the second part of Murray’s career.