The nature of metamorphism, magma compositions, the spatial distribution of plutons, and foreland sediments reflect, in part, the character and thickness of continental crust. We utilized metamorphic pressure-temperature-time (P-T-t) paths, garnet Sm-Nd ages, zircon U-Pb ages, and pluton compositions to estimate paleocrustal thickness and temporal changes in crustal magma sources in the Blue Ridge of the southernmost Appalachians. Garnet Sm-Nd ages for amphibolite-facies metamorphic rocks range from 331 ± 4 to 320 ± 3 Ma. Low- and high-Sr/Y plutons that intruded these metamorphic rocks have zircon U-Pb ages of 390 ± 1 to 365 ± 1 Ma and 349 ± 2 to 335 ± 1 Ma, respectively. Therefore, garnet growth began during regional metamorphism synchronous with or shortly after intrusion of the youngest high-Sr/Y trondhjemite plutons. Phase diagram sections and thermobarometry indicate that garnet growth initiated at ∼5.8 kbar and 540 °C and grew during temperature increases of 60–100 °C and pressure increases of 2–3 kbar. The older, low-Sr/Y magmas are inferred to have been sourced in the crust at depths <∼30 km, insufficient for garnet to be stable. However, the younger, high-Sr/Y magmas are inferred to have been sourced at >30 km depths where garnet was stable. Hafnium isotopic compositions for all the plutons, but one, exhibit a range from negative initial εHf(i) to weakly positive initial εHf(i), indicating incomplete mixing of dominantly crustal sources. Our data require minimum crustal thicknesses of ∼33 km at 331 Ma; however, Alleghanian crustal thicknesses must have locally reached 39 km, based on crustal reconstruction adding the Alleghanian thrust sheet beneath the eastern Blue Ridge. We infer the presence of hot, tectonically thickened crust during intrusion of the early Alleghanian high-Sr/Y plutons and conclude that garnet growth and plutonism reflect a progressive increase in crustal thickness and depth of magma generation. The crustal thickening was synchronous with deposition of Mississippian to early Pennsylvanian sediments in the foreland basin of the Appalachian orogen between 350 and 320 Ma. This crustal thickening may have preceded emplacement of the Alleghanian thrust sheets onto the North American craton.