Wind-driven upwelling in Pacific Panamá is a significant source of oceanographic variability in the tropical eastern Pacific. This upwelling system provides a critical teleconnection between the Atlantic and tropical Pacific that may impact climate variability on a global scale. Despite its importance to oceanographic circulation, ecology, and climate, little is known about the long-term stability of the Panamanian upwelling system or its interaction with climatic forcing on millennial time scales. Using a combination of radiocarbon and U-series dating of fossil corals collected in cores from five sites across Pacific Panamá, we reconstructed the local radiocarbon reservoir correction, ΔR, from~6750 cal B.P. to present. Because the ΔR of shallow-water environments is elevated by upwelling, our data set represents a millennial-scale record of spatial and temporal variability of the Panamanian upwelling system. The general oceanographic gradient from relatively strong upwelling in the Gulf of Panamá to weak-to-absent upwelling in the Gulf of Chiriquí was present throughout our record; however, the intensity of upwelling in the Gulf of Panamá varied significantly through time. Our reconstructions suggest that upwelling in the Gulf of Panamá is weak at present; however, the middle Holocene was characterized by periods of enhanced upwelling, with the most intense upwelling occurring just after of a regional shutdown in the development of reefs at~4100 cal B.P. Comparisons with regional climate proxies suggest that, whereas the Intertropical Convergence Zone is the primary control on modern upwelling in Pacific Panamá, the El Niño-Southern Oscillation drove the millennial-scale variability of upwelling during the Holocene.