One of the key-features in the safety assessment of geological repositories for spent nuclear fuel is the rate of radionuclide release from fuel in contact with groundwater. This process is driven by the radioactivity of the fuel itself through the radiolysis of the groundwater producing oxidative species capable of converting the fuel matrix (UO<inf>2</inf>) to more soluble U(VI). Models describing this process are often based on the spatial dose rate distribution which is derived from the radionuclide inventory (often considered to be homogeneously distributed in the fuel). However, in reality the inventory is radially distributed with higher concentrations of fission- and neutron activation products closer to the fuel pellet surface. In this work, we have explored the impact of the spatial radionuclide distribution on the dose rate profile and rate of fuel matrix dissolution using SCALE and MCNP calculations in combination with a previously developed steady-state approach for radiation-induced dissolution of UO<inf>2</inf>. When accounting for the spatial radionuclide distribution, the calculated maximum rate of dissolution is 2–3 times higher than when assuming homogeneous radionuclide distribution.