[1]: 25  The island is of volcanic origin and very mountainous, characterized by two high plateaus and several steep river valleys.

The main rivers of Santo Antão are: The tallest mountain is Tope de Coroa, reaching an elevation of 1,979 m.[1]: 25  Other high mountains on the island are Monte Tomé (1,863 m), Gudo de Cavaleiro (1,810 m), Monte Moroços (1,767 m) and Pico da Cruz (1,584 m).

The major climate risk, similarly to other Cape Verdean islands, yet much less pronounced in the higher altitudes due to better ability in gaining moisture from clouds, is drought.

The island's agriculture products include sugar cane, yams, cassava, bananas, mangoes, and grain.

Due to its mountainous nature, most of the island's plantations are done in terraces, obviating the use of machinery and requiring immense manual labor.

Recently, some experiences using drip irrigation have been taking place in order to mitigate the drought conditions.

The island is divided in three municipalities, which are subdivided into civil parishes: Santo Antão has 50 endangered species of flora which has the most number in the nation.

Several flora found in the island that are also found in some parts of the archipelago includes Aeonium gorgoneum, Artemisia gorgonum, Campanula jacobaea, the Conyza species of feae, pannosa and varia, Echium stenosiphon, Kickxia webbiana, Lavandula rotundifolia, Limonium braunii, Micromeria forbesii, Sonchus daltonii, Capeverdean navelwort (Umbilicus schmidtii) and Verbascum capitis-viridis.