The CARIACO (Carbon Retention in a Colored Ocean) Ocean Time-Series Program station, located at 10.50°N, 64.66°W, observed biogeochemical and ecological processes in the Cariaco Basin of the southwestern Caribbean Sea from November 1995 to January 2017. The program completed 232 monthly core cruises, 40 sediment trap deployment cruises, and 40 microbiogeochemical process cruises. Upwelling along the southern Caribbean Sea occurs from approximately November to August. High biological productivity (320–628 g C m−2 y−1) leads to large vertical fluxes of particulate organic matter, but only approximately 9–10 g C m−2 y−1 fall to the bottom sediments (∼1–3% of primary production). A diverse community of heterotrophic and chemoautotrophic microorganisms, viruses, and protozoa thrives within the oxic–anoxic interface. A decrease in upwelling intensity from approximately 2003 to 2013 and the simultaneous overfishing of sardines in the region led to diminished phytoplankton bloom intensities, increased phytoplankton diversity, and increased zooplankton densities. The deepest waters of the Cariaco Basin exhibited long-term positive trends in temperature, salinity, hydrogen sulfide, ammonia, phosphate, methane, and silica. Earthquakes and coastal flooding also resulted in the delivery of sediment to the seafloor. The program's legacy includes climate-quality data from suboxic and anoxic habitats and lasting relationships between international researchers.