The origin and causes of mineralogical diversity of A-type granites are debated. The series of A-type granite plutons, with distinct mineralogical differences, emplaced along an Upper Paleozoic crustal-scale shear zone in the Cobequid Highlands, Nova Scotia, provide an opportunity to examine the origin of different A-type plutons in a similar tectonic setting. Based on the ferromagnesian minerals present, the plutons are classified into sodic granites with sodic amphibole, calcic granites with calcic amphibole, and biotite granites. Sodic and calcic granites occur exclusively in complex intrusions with subequal amounts of gabbro in the eastern shear zone, whereas plutons in the western shear zone, with lesser gabbro, are solely biotite granites. Trace elements and radiogenic isotopes show that the three granite types have different sources. Intensive parameters including temperature, pressure, and water-in-melt contents were estimated from mineralogical and geochemical data. Modeling of these geochemical data suggests that the biotite and calcic granites were derived by 20%–40% partial melting of intracrustal feldspathic rocks, whereas the sodic granites are extreme fractionates (90%) of coeval mafic magma. We propose that supply of Upper Paleozoic mafic magma, probably related to regional extension and decompression melting beneath the Magdalen Basin, created a deep crustal hot zone in the eastern Cobequid Highlands, and extreme fractionation of underplated mafic sills produced the sodic granites. Heat transfer from crystallizing mafic magma induced partial melting of the surrounding crust, creating batches of biotite and calcic granitic melts in different depths. Fractionated and crustally derived melts segregated along crustal-scale faults, constructing the complex plutons in the east. Melting of the crust was further facilitated by the release of water from the crustal rocks upon heating. In the eastern shear zone, water was released predominantly by magmatic rocks and in lesser amounts compared to the west, where Neoproterozoic sedimentary and volcaniclastic rocks are more abundant. The volatile-rich granitic melts in the western part of the shear zone were crystallized rapidly, stabilizing only biotite. This study demonstrates that the mineralogical variations in A-type granites arise from rather similar magma compositions, but they are important petrogenetic indicators of varying sources, specific magmatic processes, and emplacement conditions.