High-magnitude flood events are among the world’s most widespread and significant natural hazards and play a key role in shaping river channel−floodplain morphology and riparian ecology. Development of conceptual and quantitative models for the response of bedrock-influenced dryland rivers to such floods is of growing scientific and practical importance, but in many instances, modeling efforts are hampered by a paucity of relevant field data. Here, we combined extensive aerial and field data with hydraulic modeling to document erosion, deposition, and vegetation changes that have occurred during two successive, cyclone-driven, extreme floods along a 50-km-long reach of the bedrock-influenced Sabie River in the Kruger National Park, eastern South Africa. Aerial light detection and ranging (LiDAR) data and photography obtained after extreme floods in 2000 and 2012 (discharges >4000 m3 s−1) were used to generate digital elevation models (DEMs) and provide the boundary conditions for hydraulic modeling (flow shear stresses for three discharges up to 5000 m3 s−1). For the Sabie River study reach as a whole, DEM differencing revealed that the 2012 floods resulted in net erosion of ~1,219,000 m3 (~53 mm m−2). At the subreach scale, however, more complex spatial patterns of erosion, deposition, and vegetation change occurred, as largely controlled by differences in channel type (e.g., degree of bedrock and alluvial exposure) and changing hydraulic conditions (shear stresses widely >1000 N m−2 across the river around peak flow). The impact of flood sequencing and relative flood magnitude is also evident; in some subreaches, remnant islands and vegetation that survived the 2000 floods were removed during the smaller 2012 floods owing to their wider exposure to flow. These findings were synthesized to refine and extend a conceptual model of bedrock-influenced dryland river response that incorporates flood sequencing, channel type, and sediment supply influences. In particular, with some climate change projections indicating the potential for future increases in the frequency of cyclone-generated extreme floods in eastern southern Africa, the Sabie and other Kruger National Park rivers may experience additional sediment stripping and vegetation removal. Over time, such rivers may transition to a more bedrock-dominated state, with significant implications for ecological structure and function and associated ecosystem services. These findings contribute to an improved analysis of the Kruger National Park rivers in particular, but also to growing appreciation of the global diversity of dryland rivers and the relative and synergistic impacts of extreme floods.