The good doctor set about his new venture ably assisted by wife Mary, while continuing to treat patients from the homestead he built on the estate in 1845.
He was a firm believer in handing out fortifieds (sherry and port) as part of the healing process, so it's little wonder his patient queues stretched out the door.
The family home still stands today, complete with many of the Penfolds' original furniture and possessions, and can be visited as part of the Great Grange Tour. It's terrific.
Most of the estate's original bluestone structures are also still standing, including the heritage-listed cellar where winemaker Max Schubert hid his bottles of Grange behind a false wall during the years he was forbidden to make it.
Yes, one of the most lauded wines in the world almost didn't get over the line after widespread criticism led Penfolds bosses to pull the pin on its production in 1957.
Schubert continued to make it in secret, however, and when he was told to start production again in 1960, once the world had discovered its virtues, he had to confess he'd never actually stopped.
On my visit today there are 14 barrels of last year's Grange lined up in the cellar, each valued at $314,000.
This is only a third of the annual Grange vintage, the rest being stored at Penfolds' Barossa Valley vineyard - it's split for insurance purposes.
The recipe is locked away in a safe and only two people have the combination. Grange is liquid gold.
Penfolds is only one of hundreds of winemakers in South Australia, and thanks to a law change last year it's possible to now enjoy the local product in small eateries and bars.
The new legislation introduced a class of liquor licence making it cheaper and easier to open venues with a capacity of 120 or less. Adelaide, which like any state capital has traditional pubs everywhere you look, now has pockets of coolness.
One of these is Peel St, a laneway that already has five beautiful little bars, and several others under construction.
Clever Little Tailor was one of the first small bars in the city, and its vintage lights, exposed brick, clever shelving, great music, booth seating and excellent wine list make it a great starting point for a small-bar crawl.
A short hop away is Leigh St, another cool area. Udaberri Pintxos Y Vino is a beautiful establishment dominated by dark wood and black walls, creating a sophisticated late-night atmosphere - the perfect mood for sampling some more of that excellent South Australian red wine.
Across the road is multicultural tapas bar Casablabla. A cavernous but inviting space, its excellent menu and vibrant decor draws on Spain, Morocco, Turkey, Bali and Cambodia for inspiration.
There are so many other small bars in the city that look worth investigating, but they'll have to wait for next time.
And then there's the Barossa, McLaren Vale, the Clare Valley ... You could, figuratively at least, swim very easily in red wine in this part of the world.
CHECKLIST
Getting there: Qantas connects Auckland to Adelaide via Sydney or Melbourne, with up to 10 flights daily.
The writer travelled as a guest of Tourism Australia and the South Australia Tourism Commission.
