A common assumption for the interpretation of seawater Neodymium isotopes is that the signal is a mixture of distally advected waters. A review of the local paleogeography and bedrock Nd isotopic composition (n = 712) of the largest drainage basins of the Caribbean Sea shows: (a) unradiogenic sedimentary and crystalline sequences in the cratonic-derived eastern Andes; (b) very radiogenic sequences in the western Andes and Panama Isthmus; and (c) intermediate values in between them (Cauca River drainage basin). These local signatures can be matched to the Miocene-Pliocene record of Ocean Drilling Project sites ODP-998, 999, and 1000, dating the arrival of major inter-Andean drainages to the Caribbean Sea. The birth of the Atrato River at 15 Ma, following closure of the Central American Seaway, delivered very radiogenic Nd isotopes to the Caribbean Sea (εNd: +5.5), while arrival of Magdalena River waters at 11 Ma brought very unradiogenic values (εNd << −8). Later excavation of the Cauca River canyon at ∼7 Ma added a moderately radiogenic source (εNd: +1.9), modulating Magdalena River signatures to the Caribbean Sea. Flocculates forming in tropical deltas and estuarine environments carried these signals in hyperpicnal flows to slowly mixing Caribbean bottom waters, mimicking distally advected water.