Mixed-layer illite/smectite (I/S) clays were analyzed from 22 deep exploration wells from the Jeanne d’Arc Basin on the Grand Banks offshore Newfoundland, the host of large commercial hydrocarbon accumulations discovered in the last two and a half decades. The fine fraction of the clays (<0.1 μm) consists mainly of mixed-layer I/S with minor amounts of kaolinite, illite, and chlorite. Smectite and (or) smectite-rich I/S clays were supplied to the Jeanne d’Arc Basin from Upper Jurassic to Tertiary times. Smectite-rich I/S clays occur only in shallow samples irrespective of geologic age. The proportion of illite in I/S mixed-layers, as well as the degree of ordering, increase with depth and temperature indicating that smectite-rich I/S clays have been progressively illitized in both rift and post-rift sediments of the Jeanne d’Arc Basin during burial. The transition from random to R1-ordered I/S occurs between subsurface depths of 1940 and 3720 m and crosses major stratigraphic boundaries. The transition from R1-to R3-ordered I/S generally occurs below 4000 m depth. Variable shapes of I/S depth profiles reflect the influence of temperature, fluid migration, subsidence history, basin structure, lithology, and salt diapirism on I/S diagenesis. Based on these variations, the basin can be subdivided into 4 regions with different illitization gradients. In the Southern Jeanne d’Ac Basin, advanced I/S diagenesis probably reflects uplift and denudation and (or) higher paleogeothermal gradients. Rapid increase of percent illite in I/S with depth in the Trans-Basinal Fault area is most likely controlled by upward flow of hot, K+-bearing fluids along faults. The migration of hydrocarbons probably followed the same pathways as the illitizing fluids. Delayed illitization in the Northern Jeanne d’Arc Basin and Central Ridge area reflects insufficient K+ supply because of a lack of detrital K-feldspar in the host sediment, the absence of faulting, and the presence of thick shale intervals. These findings show that I/S depth profiles may vary within the same sedimentary basin due to a variety of geological factors. Single wells generally cannot be considered representative for the basin as a whole.