The home favourite entered the final day at Leopard Creek Country Club three shots off the lead and despite making a double and a bogey on the front nine to turn in 35, he had trimmed that gap to one at the turn.
As the rest of the leading contenders fought for their maiden victories, Bezuidenhout then used all of his experience to card three birdies on the way home in a 69 to finish at 14 under, clear of England's Richard Bland, American Sean Crocker, Pole Adrian Meronk and South African Jayden Schaper.
Bezuidenhout's route to the top has been a remarkable one, as he revealed in a European Tour Player Blog in March of last year.
He nearly died after accidentally drinking rat poison as a child, an event that saw him develop a stutter and anxiety, the medication for which led to him being handed a ban as an amateur.
Bezuidenhout was cleared of using any form of drug to enhance his performance, but his nine month exile from the game meant he missed the Eisenhower Trophy.
Those experiences have not held him back, however, with his victory at the 2019 Estrella Damm N.A. Andalucía Masters hosted by the Sergio Garcia Foundation handing him a Major debut at The Open Championship, and he has now played in all of golf's four biggest events, finishing in the top 40 in his first appearance at the Masters Tournament earlier this month.
And after claiming that win at real Club Valderrama, Bezuidenhout can now add a triumph on another of the European Tour's great stages to his CV.
"It's incredible," he said. "This tournament has been close to my heart since I played it for the first time. It's always been a tournament I wanted to win and to pull it off today is really, really special to me.
"I'm proud of myself to stick in there and to have pulled it off round here.
"I played with Louis (Oosthuizen) and Charl (Schwartzel) in a practice round at Augusta and they said you can't play this course the way you played it with the previous grass on it. I never thought of it that way and I just came here with a different frame of mind and I played it like it's playing now - firm and fast."
Schaper chipped in at the second to join the lead and he held it on his own after overnight leader Meronk found water off the tee at the fifth, holing a long putt to keep the damage to one shot.
Bezuidenhout had holed a 30 footer on the third and after making an impressive par save on the fourth, he put his tee shot to 12 feet on the fifth and got up and down from the sand on the sixth to join the lead.
A double followed on the next when he put his tee shot in the water but he was just one back as Schaper and Meronk both made bogeys after missing the green.
Crocker took advantage of the par five second and short par four sixth - with a dropped shot at the third - before a brilliant drive set up just the second birdie of the day on the tough ninth and he was just one back.
That soon became a share of the lead as Schaper sent his tee shot left at the tenth, needed a drop, and then three putted for a triple bogey.
Just like on day three, Meronk had turned in 37, but he got up and down from the sand on the short par four 11th to take the lead on his own, with Bezuidenhout also taking advantage from six feet to get back to 12 under after a bogey on the eighth.
There was then a two shot swing on the 13th, with Crocker making the most of the par five and Meronk dropping a shot after going a long way left off the tee.
A 25 footer from Bezuidenhout on the 14th moved him to the top of the leaderboard as Crocker bogeyed the 15th after being forced to lay up and failing to get up and down from the sand.
And the 26-year-old led by two as he laid up on the 15th and put his approach to 18 feet for another birdie.
Crocker was just one back when he birdied the 17th but he went out of bounds on the last after hitting a buggy and then found water for a triple bogey and a 72.
Schaper carded three birdies and three bogeys in his last eight holes in a 75, while Meronk sandwiched a birdie on the 15th with a double on the 14th and a bogey on the last in his 76.
Bland made four birdies and two bogeys in a 70 that handed him a second consecutive top ten and saw him finish a shot clear of countryman Marcus Armitage, Spaniard Adri Arnaus, Scotland's Scott Jamieson and Robert MacIntyre, and Frenchman Alexander Levy.