The tropical Pacific ocean–atmosphere system influences global climate on interannual, decadal, as well as longer timescales. Given the uncertainties in the response of the tropical Pacific to increasing greenhouse gasses, it is important to assess the role of the tropical Pacific climate variability in response to past global changes. The Peruvian Upwelling Ecosystem (PUE) represents an ideal area to reconstruct past changes in the eastern tropical Pacific region because productivity and subsurface oxygenation are strongly linked to changes in the strength of the Walker circulation. Throughout the last 2000 years, warmer (the Roman Warm Period – RWP; the Medieval Climate Anomaly – MCA; and the Current Warm Period – CWP), and colder (the Dark Ages Cold Period – DACP – and Little Ice Age – LIA) intervals were identified in the Northern Hemisphere (NH). We use a multi-proxy approach including organic and inorganic proxies in finely laminated sediments retrieved off Pisco (~14° S), Peru to reconstruct the PUE response to these climatic periods. Our results indicate that the centennial-scale changes in precipitation are associated with changes in the Intertropical Convergence Zone (ITCZ) meridional displacements and expansion/contraction of the South Pacific Sub-tropical High (SPSH). Additionally, during the NH cold periods, the PUE exhibited an El Niño-like mean state, characterized by a weak oxygen minimum zone (OMZ), and low marine productivity. In contrast, during the RWP, the last stage of the MCA and the CWP, the PUE exhibited a La Niña-like mean state, characterized by an intense OMZ and high marine productivity. Comparing our results with other relevant paleoclimatic reconstructions revealed that changes in the Walker circulation strength and the SPSH expansion/contraction controlled marine productivity and OMZ intensity changes during the past two millennia.