In the Humboldt Current System (HCS), biological and non-biological components, ecosystem processes, and fisheries are known to be affected by multi-decadal, inter-annual, annual, and intra-seasonal scales. The interplay between atmospheric variability, the poleward undercurrent, the shallow oxygen minimum zone (OMZ), and the fertilizing effect of coastal upwelling and overall high primary production rates drive bio-physical interactions, the carbon biomass, and fluxes of gases and particulate and dissolved matter through the water column. Coastal upwelling (permanent and seasonally modulated off Peru and northern Chile, and markedly seasonal between 30°S and 40°S) is the key process responsible for the high biological productivity in the HCS. At present, the western coast of South America produces more fish per unit area than any other region in the world ocean (i.e. ∼7.5 × 10 6 t of anchoveta were landed in 2007). Climate changes on different temporal scales lead to alterations in the distribution ranges of anchoveta and sardine populations and shifts in their dominance throughout the HCS. The factors affecting the coastal marine ecosystem that reverberate in the fisheries are crucial from a social perspective, since the economic consequences of mismanagement can be severe. Fish remains are often well-preserved in sediment settings under the hypoxic conditions of the OMZ off Peru and Chile, and reveal multi-decadal variability and centennial-scale changes in fish populations. Sediment studies from the Chilean continental margin encompassing the last 20,000 years of deposition reveal changes in sub-surface conditions in the HCS during deglaciation, interpreted to include: a major reorganization of the OMZ; a deglacial increase in denitrification decoupled from local marine productivity; and higher deglacial and Holocene paleoproductivities compared to the Last Glacial Maximum in central-south Chile (35-37°S) while this scheme is reversed for north-central Chile. Multi-scale, interdisciplinary approaches and focused research groups are needed to understand air-sea interactions, plankton dynamics, biomass removal by fisheries, and the transformation and fluxes of matter across the different HCS components. In this paper, we present a multidisciplinary synthesis of the HCS that covers its physics, atmosphere, primary and secondary production, medium and high trophic levels, fisheries including management aspects, and relevant sedimentary studies.