The 30-year-old carded a final-round 66 for a three-shot triumph over South Africans Shaun Norris (68) and Thriston Lawrence (63) and Jordan Smith (68) from England.
Play was suspended for 150 minutes from mid-afternoon due to a thunderstorm at Glendower Golf Club, and Manassero had teed off on the par-five 17th when the hooter sounded.
But the Italian kept his composure to end a long title drought since winning for a fourth time on the Tour at the BMW PGA Championship at Wentworth.
Since those halcyon early seasons of his career, Manassero has struggled and was relegated to the second-tier European Challenge Tour before regaining European Tour status.
In the autumn gloom of the South African financial capital, the native of Verona was smiling again and said his fifth European victory brought “overwhelming joy”.
“I have been on a crazy journey of ups and downs in my golf career, and in recent seasons I have had a lot more bad days than good ones,” he said.
“I never lost faith in my ability to recover, though, and am so happy to hold this trophy. It means the world to me.
“I cannot really reflect right now on how special today is in my life — this success is going to take some time to sink in.
“My final round contained a lot of good shots, and to finish with four straight birdies was fantastic.
“Winning by three shots might suggest is was comfortable, but nothing could be further from the truth.”
Manassero, who at 17 became the youngest winner of a European title, birdied seven holes in his final round, with the sole blemish a bogey four at 12.
Four-time European Tour champion Lawrence fired a 63 — the equal lowest round of the day — that included two eagles, six birdies and one bogey.
1Athletic Club6510112916DResult DrawWResult WinWResult WinWResult WinWResult WinWResult Win2Lazio5410112913No ResultWResult WinWResult WinWResult WinWResult Win
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