Englishman Nixon's perfect pitch on the par-five eighth at the Glendower Golf Club, on the outskirts of Johannesburg, saw him finish with a 64, one shot ahead of Italian Marco Crespi and South Africa's Jbe Kruger.
Crespi, starting on the back nine, hit four straight birdies and carded an eagle, when he holed from the fairway on the 444-yard seventh.
Kruger also hit an eagle in his round of 65.
South African Retief Goosen, back in contention after long-standing back problems, hit seven birdies in a six-under 66 for a share of fourth place with Christian Basson.
The 44-year-old Goosen, a two-time U.S. Open winner, said he had been pain free for the last month.
"I have started to feel we can start going after the ball now, it's just a question of getting some consistency going," he told reporters.
Home golfers have won 11 of the last 13 South African Open titles but top-ranked South African Charl Schwartzel, who was Masters champion two years ago, has not been among them.
He put himself in early contention as he did not drop a shot in his 67 for a share of sixth place with three other golfers - one of them his younger brother Attie.
Thursday's play marked the first day of the start of the 2014 European Tour.
(Reporting by Mark Gleeson; Editing by Justin Palmer)
