We present new major element and isotopic (Nd–Sr–Hf–Pb) data and modelling from alkaline rocks of the Monteregian Igneous Province of southern Quebec (Canada) that constrain the mantle source and the magmatic origin of these rocks. The whole-rock chemical composition of the intrusions is consistent with fractional crystallization of an assemblage of olivine ± clinopyroxene (± plagioclase) derived from ocean island basalts (OIB)-like magmas, and variations in the Sr and Nd isotope compositions suggest as much as 20% crustal contamination. The bulk of the Nd–Sr–Hf and Pb isotopic data form a tight cluster between a depleted mantle end-member (HIMU, high-U/Pb mantle) and an enriched mantle (EMI) end-member and are thought to reflect a sub-continental lithospheric mantle that was metasomatized by a convecting asthenospheric plume. Variations in these isotopic compositions along the west–east axis of the Monteregian Province (from the Oka carbonatite to the Mount Shefford intrusion) may reflect various degrees of mixing between HIMU and EMI enriched mantle reservoirs. Anomalously low 207Pb/204Pb and 208Pb/204Pb isotopic ratios from some of the intrusions likely indicate incorporation of an Archean component within the lithospheric mantle. We propose a model in which Monteregian magmatism formed from melting of a predominantly Proterozoic metasomatized lithospheric mantle in response to lithospheric extension during the opening of the North Atlantic Ocean at ca. 124 Ma.