The Argentine, who first fell in love with the game as a child when he used to dive into ponds to retrieve lost balls, finally got his hands on the Claret Jug in 1967 - 19 years on from his Open debut.
At 44, he became the second oldest Champion Golfer of the Year and was just two years younger than Old Tom Morris was when he won his fourth and final title 100 years earlier.
For De Vicenzo, that Saturday afternoon at Hoylake in July of 1967 was the reward for a lifetime of perseverance.
He recorded 10 top-10 finishes in Majors before his first win, plus appearances in the round of 16 and quarter-finals of the PGA Championship, back when it was a match-play Major.
De Vicenzo competed for the game's biggest prizes for more than two decades and straddled different eras. His first Open saw him challenge Henry Cotton for the Claret Jug, while in 1967 he battled Jack Nicklaus, Gary Player, Tony Jacklin and Peter Thomson.
His longevity - and several heart-breaking near-misses - certainly contributed to the warm reception he received from the Hoylake gallery.
But he was also renowned for possessing one of the finest swings in the game. Golf Digest once described it as a "drowsy" swing and De Vicenzo sagely explained: "If you hurry, then nothing seems to go right."
It was an action that endured and a key reason why De Vicenzo was so successful for so long. He won more than 200 tournaments worldwide and the World Cup with Argentina in 1953. However, his win at The 96th Open will always be the one that stands out above all else.
De Vicenzo finished third five-times at The Open before finally cracking the code, making the podium in 1948, 1949, 1956, 1960 and 1964, while he was also second in 1950.
At the height of the swinging sixties, it was thought his best days were behind him and golf, gripped by the likes of Nicklaus and Player, had moved on.
However, he made a solid start at Royal Liverpool in 1967 and sat just one shot off the lead at halfway, thanks to rounds of 70 and 71.
Conditions for the third round were favourable and suited a player with De Vicenzo's effortless swing. Just minutes after Player had set a new course record, De Vicenzo equalled it with a sensational 67 and he took a two-shot lead over the South African into the final round.
Player faded from contention on the final day but Nicklaus, seeking to defend the title he had won 12 months before, stayed with the pace set by De Vicenzo.
Nicklaus, who so often produced his best golf in the biggest moments, scored 69 on the final day for a total of 280 - but De Vicenzo would not be denied. Not this time.