High-resolution sediment records from the eastern tropical North Pacific (ETNP) spanning the last ~240 ka B.P. were studied to document the nature of millennial-scale climatic events in the tropical Pacific and to investigate teleconnection mechanisms. We present organic carbon (%OC) and diffuse spectral reflectivity records as indicative of upwelling and productivity changes off NW Mexico over the middle to late Pleistocene. The new productivity records document the persistence of abrupt millennial-scale changes over the last two glacial cycles. Detailed spectral and wavelet time series analyses show the predominance of longer climatic cycles (2–6 ka) during the last and the penultimate glacial periods. The persistence of millennial variability during the penultimate glacial, in absence of large ice rafted debris events in the North Atlantic, suggests that freshwater input through ice sheet dynamics is not essential for millennial-scale climate variability. Given the worldwide emerging picture of remarkable similar millennial-scale records over long time periods, we suggest that the pacing of this climate variability may represent a natural resonance in the climate system, amplified by a tightly coupled oceanic and atmospheric teleconnection processes. We present a schematic scenario of millennial-scale climate change depicting the role of the tropical Pacific in this global teleconnection system by linking productivity and upwelling changes in the ETNP with shifts in the position of the Intertropical Convergence Zone and the strength of the subtropical North Pacific High.