In a modeling sensitivity study we investigate the evolution of the ocean circulation and of marine carbon isotope (δ13C) records during the Miocene (about 23–5 million years ago). For this purpose we ran an ocean-circulation carbon cycle model of intermediate complexity (Large Scale Geostrophic– Hamburg Ocean Carbon Cycle Model, version 2s) exploring various seaway configurations. Our investigations confirm that the Central American Seaway played a decisive role in the history of the Miocene ocean circulation. In simulations with a deep Central American Seaway (depth range 1–3 km), typical for the early to middle Miocene, deep water production in the North Atlantic is absent or weak, while the meridional overturning circulation is dominated by water mass formation in the Southern Ocean. Deep water formation in the North Atlantic begins when the Central American Seaway shoals to a few hundreds of meters, which is typical for the late Miocene. Our results do not support ideas that the mid-Miocene closing of the Eastern Tethys contributed to Antarctic glaciation. On the other hand, we find some water exchange between the Indian Ocean and the Atlantic via the Eastern Tethys during the early Miocene. Our model results for the Atlantic meridional overturning circulation and for Atlantic δ13C during the late Miocene are largely independent from depth variations of the Greenland-Scotland Ridge. To a large extent, the evolution of Miocene deep-sea δ13C records can be explained with large-scale ocean circulation changes. Our model-data comparison for the middle and early Miocene suggests that during the early Neogene the seaway effect on benthic δ13C may have been superimposed by further factors such as climate regime shifts and/or terrestrial carbon cycle changes.