The Canadian pressure-tube super critical water-cooled reactor (PT-SCWR) is an advanced generation IV reactor concept which is considered as an evolution of the conventional Canada Deuterium Uranium (CANDU) reactor that includes both pressure tubes and a low temperature and pressure heavy water moderator. The Canadian PT-SCWR fuel assembly utilizes a plutonium and thorium fuel mixture with supercritical light water coolant flowing through the high-efficiency re-entrance channel (HERC). In this work, the impact of fuel depletion on the evolution of lattice physics phenomena was investigated starting from fresh fuel to burnup conditions (25 MW d kg−1 [HM]) through sensitivity and uncertainty analyses using the lattice physics modules in standardized computer analysis for licensing evaluation (SCALE). Given the evolution of key phenomena such as void reactivity in traditional CANDU reactors with burnup, this study focuses on the impact of fission products, 233U breeding, and minor actinides on fuel performance. The work shows that the most significant change in fuel properties with burnup is the depletion of fission isotopes of Pu and the buildup of high-neutron cross section fission products, resulting in a decrease in cell k∞ with burnup as expected. Other impacts such as the presence of protactinium and uranium-233 are also discussed. When the feedback coefficients are assessed in terms of reactivity, there is considerable variation as a function of fuel depletion; however, when assessed as Δk (without normalization to the reference reactivity which changes with burnup), the net changes are almost invariant with depletion.