The Rio Santo Antônio in Minas Gerais rises in the Espinhaço Mountains in the district of Santo Antônio do Cruzeiro, within the city of Conceição do Mato Dentro. From there it runs eastward for approximately 287 km before emptying into the Rio Doce. The river drains a basin that includes several municipalities in the region.

The character of the river is defined largely by its rocky course, which produces a number of waterfalls along its length. Among the most notable are Bahia Falls and Tabuleiro Falls, the latter of which was rated the most beautiful waterfall in Brazil in the 2005 edition of the Guia 4 Rodas. Paddlers should be aware that this rocky, waterfall-punctuated terrain means significant gradient changes and likely technical or impassable sections, particularly around the falls themselves.

The river has a history of human use stretching back to the colonial era, when bandeirantes traveled it as a transportation corridor during the Brazilian Gold Rush. Today it sees use for fishing, gold panning, and general leisure and tourism activity, suggesting some degree of public access and familiarity with the waterway among locals.