The licence question
Your ordinary national licence is valid in South Africa if it's printed in English and carries a photograph. If it isn't, you need an International Driving Permit, and the 1949-convention version is the one rental desks ask for. A photo on your phone won't do. Carry the physical card.
Left-hand drive, and the first day
You drive on the left. The instinct arrives within an hour on a quiet road; most people find it clicks on a rural stretch rather than in city traffic. Two things take longer. The indicator stalk is on the right, so you'll wash the windscreen instead of indicating for the first day. And roundabouts flow clockwise. Give way to traffic already on the circle, coming from your right.
Manual or automatic
The rental fleet is overwhelmingly manual. Automatics exist but they're a smaller pool, and they book out first over Christmas, Easter, and South African school holidays. Reserve one weeks ahead if you want one, and expect roughly ZAR 150 to 300 a day more. If you can drive a manual, take one. More choice, lower cost, and you'll rarely sit in stop-start traffic long enough to make it tiring.
The car you actually need
A standard hatchback or sedan handles roughly 90% of what a visitor wants to do. Cape Town, the Winelands, the Whale Coast, the Garden Route, the Panorama Route, and self-drive Kruger are all sedan roads. You only need a 4x4 for genuine gravel: the Swartberg Pass in wet weather, deep Cederberg tracks, the Sani Pass (where a 4x4 is mandatory and a guided tour is the smarter choice anyway), and a handful of KZN and Kalahari reserves. Don't rent a 4x4 "just in case." It doubles the cost, you'll never use low range, and on most graded gravel a sedan at a sensible speed is fine.
Speed, fuel, and tolls
Limits are 60 in towns, 100 on rural roads, 120 on freeways. Cameras are common, and fines can chase you home through the rental company with an admin fee attached. Fuel is full-service: an attendant pumps, you pay by card or cash, and a few rand is a fair tip. The major freeways, the N1, N3, and the Gauteng network, are tolled. The scenic routes you came for mostly aren't.
Where driving earns its keep
The Western Cape is a self-drive masterpiece. Cape Town to the Winelands in under an hour, the Whale Coast in two, the Garden Route strung out over a few unhurried days. The Panorama Route around Kruger is a half-day of genuinely world-class scenery. Self-drive Kruger itself is one of the best-value safaris on earth: your own car, your own pace, your own picnic, and the park's roads are sedan-friendly.
Where driving is a mistake
Cape Town to Kruger is 14 to 16 hours of flat, unremarkable interior. Fly it: two and a half hours, and you save a day on either end. Johannesburg and Durban city centres after dark: take an Uber rather than a rental car. And any plan under about ten days that tries to span both coasts will spend the trip in the car and remember only the motorway.
The safety picture
Daytime driving between tourist nodes is normal and low-risk; millions do it. The risks that actually matter are three.
Smash-and-grab theft at city intersections. Keep bags off the seats and the windows up.
Arriving somewhere unfamiliar after dark. Plan the route so the last leg is in daylight, and use a lit, attended car park in cities.
And the one people underweight: animals and unlit roads after dark outside towns. Don't drive at night between towns if you can avoid it, not primarily for crime but because livestock, antelope, and pedestrians on dark roads are genuinely dangerous. Use Google Maps, but don't blindly follow a "fastest" route into an area you can't identify. Cross-check against current local advice.
Insurance and the gravel-road catch
Collision damage waiver lowers your excess but rarely to zero. The zero-excess upsell is more worth it here than in Europe, because of stone-chip windscreens on gravel and the adjustment to left-side driving. Read the one line that matters: whether the policy covers gravel roads. Many exclude them, and a cracked windscreen on the Swartberg is then yours to pay for.
One more thing
Fuel stations are few and far between in the Karoo, the Northern Cape, and the long stretches of the N1 and N2 away from towns. Fill up when you can, not when you have to. A half-empty tank in the Karoo at dusk is the moment you remember you meant to fill up two towns ago.