The Port Mouton pluton is unique among the Late Devonian peraluminous granitoid bodies in the Meguma Lithotectonic Zone of southwestern Nova Scotia in its lithological heterogeneity, extensive physical and chemical interaction with the country rocks, clear evidence for mingling and mixing with mafic magmas, and highly abundant pegmatites. New U–Pb age determinations on monazite establish an intrusion age of 373 ± 1 Ma, similar to the ages of other Meguma Lithotectonic Zone granitoid plutons and mafic intrusions. Field relations, petrology, and geochemistry define three stages of intrusion of the Port Mouton pluton: (i) early stage, discontinuously exposed around the outer margin of the pluton, dominated by coarse-grained tonalite–granodiorite, and with Rb/Sr < 0.55, Eu/Eu* > 0.40, and GdN/LuN <2; (ii) middle stage, occupying the interior of the pluton, dominated by medium-grained granodiorite–monzogranite, and with Rb/Sr > 0.55, Eu/Eu* < 0.40, and GdN/LuN > 2; and (iii) late stage, consisting of abundant minor sheets throughout the pluton, dominated by fine-grained tonalite, granodiorite, and leucogranite that are similar to rocks of the early and middle stages. The Port Mouton pluton shows a wider range of 87Sr/86Sri (0.7036–0.7154), and a wider range and generally higher εNdi (–3.72 to +2.12), than other granitoid rocks in the Meguma Lithotectonic Zone, potentially reflecting a complex, partially equilibrated, interaction among mantle, lower crust, and upper crust. Field, petrological, and chemical evidence for the involvement of mantle-derived magmas and melting of upper crust permit modelling of the Port Mouton pluton granitoid compositions by three simultaneous mixing equations. These mixing model results suggest that the early stage granitoid rocks can form from simple three-component mixing relationships when the bulk distribution coefficients between residuum and melt for Sr and Nd range from 1.05 to 1.18, or two-component mixing combined with fractionation of material like the known felsic lower crust. The middle stage granitoid rocks only yield solutions involving two-component mixing and fractionation of material unlike the known felsic lower crust. We conclude that the Late Devonian mafic magmas played a major role in the formation of granitoid magmas in the Meguma Lithotectonic Zone by supplying heat and material to cause partial fusion of the Avalon lower crust.