Geochemical and Nd isotopic data from mafic and newly discovered ultramafic rocks in the Adirondack Lowlands suggest widespread enrichment of the lithospheric mantle under the Grenville Province. Incompatible element abundances and previously published Hf TDM (zircon) (depleted mantle model age) and Nd TDM ages from rocks of the anorthosite-mangerite-charnockite-granite suite in the Adirondack Highlands document similar enrichment in the lower crust and its strong influence on subsequent magmatic events throughout the Ontario-Quebec-Adirondack segment of the Grenville Province. Likely the consequence of long-lived (ca. 1.4–1.2 Ga) northwest-directed subduction along the southeast edge of Laurentia (previously proposed Andean margin), this enrichment is similar to that associated with the vast (>240,000 km2) ultrapotassic province of the western Churchill Province. Enrichment of the lithospheric mantle beneath orogenic belts is a predictable and important differentiation process that has operated on Earth for at least the past 3 b.y.