Human pressures and loss of natural fish habitats led to a decline in fish populations in terms of abundances, biodiversity, and average size in sub-Sahelian Burkina Faso. Little knowledge exists about fish assemblages regarding their composition, their habitat preferences, or their sensitivity to or tolerance of human pressures. This research provides the first data-driven basis for sustainably managing fish and associated aquatic and terrestrial habitats. Surveys in four different regions sampled 18,000 specimens from 69 species during the dry season. Fish communities, available abiotic habitat conditions, habitat use, and human pressures were assessed and analyzed. Fish communities cluster into four distinct types, each dominated by either Cichlidae, Clariidae, Cyprinidae, or Alestidae and accompanied by specific other families and genera of fish. Habitat preferences of four key species (Labeo coubie, Bagrus bajad, Chelaethiops bibie, and Lates niloticus) were linked to ecological habitat conditions. Results show that physical parameters influence fish community composition and abundances and, when indexed according to pressure type, are linked to responses in fish metrics. Relative abundance either dropped (Mormyridae) or increased (Cichlidae, Cyprinidae) with rising pressure intensity, and some sentinel taxa (Auchenoglanis, Hydrocynus) were only found in low-pressure sites. The outcomes of this study provide basic knowledge of habitat availability, habitat use by fish, species associations, and human pressures and therefore provide the basis for effective conservation and management of fish populations.