The purpose of the study was to examine the extent to which drainage morphology has been influenced by faulting, folding and bedrock lithology in the Cape Fold Belt (CFB) of South Africa. This region was formed during Paleozoic–Mesozoic convergence along the south-western margin of Gondwana. An extensive structural geology database, terrain characteristics and stream network data were analysed using Geographical Information Systems (GIS) to examine the possible linkages between structure and fluvial drainage. Results indicated that the contemporary geomorphology of the area reflects the influence of folding and faulting as well as differential erosion. The following drainage anomalies suggestive of strong structural control were identified: orientation of flow direction of major streams corresponding to structural lineaments, abrupt changes in stream direction influenced by anticline fold axes, faults and joints, and fault-aligned streams. Drainage development in the study area responded noticeably to the underlying structure. The study raises questions with regard to the implications of one major or multiple dominant structural controls on drainage morphology and pattern. The findings have relevance with regard to the understanding fluvial drainage development and landform evolution in tectonically deformed regions.