Crustal structure in South America is one of the least understood among the Earth's continental areas. Variations in crustal thickness are still poorly constrained over large portions of the continent because of scarce or unevenly distributed crustal thickness estimates throughout South America. To address this scarce and inhomogeneous data cover we explore the possibility to derive crustal thickness from satellite gravity data. In this study, we utilize the combined gravity model EIGEN-6C, which is composed of GOCE and other gravity data. The Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite has a much more uniform spatial resolution than any land-based gravity or seismic survey in South America. The gravity data inversion is for a simple two-layer model with fixed density contrast over the interface, the Moho. The method is not relying on point constraint data and assumes that all of the signal is related to topography of the Moho. Model quality can therefore be assessed by a comparison with point observations on crustal thickness. We show that for the stable part of the continent 90% of our estimates are similar, within error bounds, to seismic observations. Variations occur in active orogenic zones or regions with suspected non-standard Moho density contrasts. A comparison with seismological models shows a high correlation with the most recent model. Especially in areas where continental and global models of crustal structure have limitations in terms of wave paths or point constraints the gravity based model provides a unique continuity of crustal structure providing new insights on structure and tectonics and increase our understanding of the Earth's structure underneath South America.