Cell to pack design concept for energy storage in automotive applications leads to a substantially increased cell size that results in temperature gradients over the surface induced by non-uniform heat transfer linked to the cooling system design, which influences the cell performance. In this paper, temperature gradient effects on life performance of a large-format cell are experimentally investigated, using a developed device that can actively control appropriate gradients in the longitudinal direction and simultaneously measure the heat generation rate (HGR). Performances under uniform and non-uniform temperature conditions (MMM: uniform temperature, LMH: low-mean-high, HLH: high-low-high) are compared and quantified. At beginning of life (BOL), the lowtemperature regions in the HLH and LMH conditions dominantly limit the cell capacity, and the HLH condition suppresses the HGR at high C-rates. During aging, the cell experiences a larger capacity fade and HGR increase under the HLH than MMM condition. The analyses of half coin cell, differential capacity (dQdV), dynamic resistance and impedance reveal that the attributing mechanisms are mainly the loss of Cathode active material, potentially the loss of lithium inventory, and the increase of impedances, indicating the electrochemically promoted side reactions and corrosions in the high-temperature regions of the HLH condition.