The main Karoo Basin of South Africa is a Late Carboniferous–Middle Jurassic retroarc foreland fill, developed in front of the Cape Fold Belt (CFB) in relation to subduction of the palaeo‐Pacific plate underneath the Gondwana plate. The Karoo sedimentary fill corresponds to a first‐order sequence, with the basal and top contacts marking profound changes in the tectonic setting, i.e. from extensional to foreland and from foreland to extensional, respectively.Sedimentation within the Karoo Foreland Basin was closely controlled by orogenic cycles of loading and unloading in the CFB. During orogenic loading, episodes of subsidence and increase in accommodation adjacent to the orogen correlate to episodes of uplift and decrease in accommodation away from the thrust‐fold belt. During orogenic unloading the reverse occurred. As a consequence, the depocentre of the Karoo Basin alternated between the proximal region, during orogenic loading, and the distal region, during orogenic unloading. Orogenic loading dominated during the Late Carboniferous–Middle Triassic interval, leading to the accumulation of thick foredeep sequences with much thinner forebulge correlatives. The Late Triassic–Middle Jurassic interval was dominated by orogenic unloading, with deposition taking place in the distal region of the foreland system and coeval bypass and reworking of the older foredeep sequences.The out of phase history of base‐level changes generated contrasting stratigraphies between the proximal and distal regions of the foreland system separated by a stratigraphic hinge line. The patterns of hinge line migration show the flexural peripheral bulge advancing towards the craton during the Late Carboniferous–Permian interval in response to the progradation of the orogenic front. The orogenward migration of the foreland system recorded during the Triassic–Middle Jurassic may be attributed to piggyback thrusting accompanied by a retrogradation of the centre of weight within the orogenic belt during orogenic loading (Early Middle Triassic) or to the retrogradation of the orogenic load through the erosion of the orogenic front during times of orogenic unloading (Late Triassic–Middle Jurassic).