Leipoldt was born in Worcester in the Cape Colony, the son of a preacher of the Nederduits Gereformeerde Kerk in Clanwilliam and grandson of Johann Gottlieb Leipoldt, the Rhenish missionary who founded the village of Wupperthal in the Cederberg mountains. His mother, Anna Meta Christiana Esselen, was the daughter of another Rhenish missionary. The church ran deep in the family, but Leipoldt's path diverged early. Educated largely at home, he was still a young man when the Second Boer War erupted across South Africa in 1899, and he became a reporter, witnessing firsthand the suffering that would fuel his most powerful poetry. The war gave him subject matter. It also gave him restlessness. Between 1902 and 1907, funded by the botanist Harry Bolus, Leipoldt studied medicine at Guy's Hospital in London and traveled through Europe, America, and the East Indies.

For six months in 1908, Leipoldt served as the personal physician of Joseph Pulitzer, the American newspaper magnate, aboard Pulitzer's yacht. It was the kind of detour that characterized his life -- improbable, brief, and followed by something entirely different. He worked as a school medical doctor in London, then became Medical Inspector of Schools in the Transvaal and later the Cape Province. He tried journalism again in 1923 before finally settling into paediatric practice in Cape Town in 1925, where he remained for the rest of his life. He never married. The restlessness that took him from the Cederberg to London to Pulitzer's yacht eventually resolved into a quieter existence, though his pen never rested.

Leipoldt wrote in Afrikaans at a time when the language was establishing itself as a literary medium. Alongside Jan F. E. Celliers and J. D. du Toit, he was one of the leading figures of the Second Afrikaans Movement, which championed Afrikaans as a language capable of serious art. Afrikaans literature emerged within a complex colonial and racial context, and Leipoldt's own work reflected that complexity -- his poetry addressed the suffering caused by the Boer War, the landscapes and legends of the Hantam district north of Cape Town, and the culture and values of the Cape Malay community. Most of his work does not translate well into English, rooted as it is in the sounds and rhythms of a language shaped by the particular mix of Dutch, indigenous, and Malay influences that produced it. His poem "The Worst Horror," a meditation on loss and the impossibility of reaching the dead, survives in translation as a glimpse of his emotional range.

Leipoldt's output beyond poetry was staggering. He published Common-Sense Dietetics in 1911, a book the British Medical Journal praised as "lively and entertaining" while doubting whether all his opinions were grounded in personal experience. He wrote The Belly Book: Or Diner's Guide in 1936, Bushveld Doctor in 1937, and posthumously, 300 Years of Cape Wine and Leipoldt's Cape Cookery. A genus of flowering plants, Leipoldtia, was named in his honor by the botanist L. Bolus in 1927. The C. Louis Leipoldt Medical Centre in Cape Town bears his name, as does a primary school in Centurion. But it is the grave in the Pakhuis Pass that captures the man most fully -- his deep love for the Hantam and the Cederberg, his connection to a landscape his grandfather helped settle, and the quiet company of San rock art painted on the sandstone above his resting place centuries before he was born.