In 1903, du Toit was appointed as a geologist within the Geological Commission of the Cape of Good Hope, and he began to develop an extensive knowledge of the geology of southern Africa by mapping large portions of the Karoo and its dolerite intrusions, publishing numerous papers on the subject.
In 1923, he received a grant from the Carnegie Institution of Washington, and used this to travel to eastern South America to study the geology of Argentina, Paraguay and Brazil.