From the southern coast of Peru to the central-north coast of Chile (18°-31°S) previous evidence suggests that wide variations in sea surface temperature (SST) over the Holocene may be associated with changes in coastal upwelling regimes along the region. Support for spatial contrasts and similarities in oceanographic dynamics comes from earlier work at both extremes of the region. Using a 12 kyr record derived from shell midden archaeological sites around Taltal Chile (25°S), we show that changes in the region are not necessarily consistent with a simple latitudinal gradient. Using δ13C and δ18O isotopic records from archaeological carbonate shells of the keyhole limpet Fissurella maxima we find that cold SST during the Early Holocene was associated with more negative δ13C values in agreement with observations from southern Peru. Warmer waters during the beginning of the Middle Holocene, had positive δ13C values, differentiating them from southern Peru and central-north Chile records. The rest of the Middle Holocene showed a decreasing SST accompanied by negative δ13C values, and after 4000 cal yr BP, the Late Holocene showed a progressive increase in SST and positive δ13C values. Finally, modern carbonate shells of F. maxima indicate a situation not observed throughout the Holocene period: warm SST is associated with negative δ13C values, in line with results on modern shells from southern Peru and modern oceanographic patterns that indicate an intensification of coastal upwelling with events of warm water intrusion. Our results show that the southern coast of the Atacama Desert experienced important fluctuations in SST and upwelling conditions during the Holocene, which may have affected the distribution of nearshore fisheries along the Northern Coast of Chile.