Lithium ion batteries (LIBs) are an indispensable component of personal electronics, electric vehicles, and back-up power source for many critical infrastructures. A series of kinetic processes occur at different length scales within LIBs during their operation. Spatially non-uniform reaction resulting from these processes may lead to inferior performance and even degradation or failure of LIBs. This thesis aims to quantitatively understand the nature of such inhomogeneous phenomena during the operation of LIBs and identify effective ways to prevent their occurrence. At the electrode level, we introduce an analytical model to predict the rate performance of LIBs when reaction non-uniformity results from kinetic limitation in electrolyte transport. The model is built upon the assumption of two prototypical reaction behaviors, uniform vs moving zone reaction, which are idealized based on observations from pseudo two-dimensional (P2D) simulations. Predictions of the analytical model exhibit high accuracy over a wide range of battery design parameters with a computational speed-up of more than 105 times compared to P2D simulations. The model also offers valuable insights on the effects of electrode reaction behavior and cell format (half vs full cells) on the battery cell performance. The analytical model is subsequently applied to optimize battery cell configurations with different objectives, and further extended to consider concentration-dependent electrolyte diffusivity and electrodes with spatially varied properties. Next, we employ a simplified circuit model to elucidate the thermodynamic origin of the reaction heterogeneity within porous electrodes. It is found that the state-of-charge (SOC) dependence of the equilibrium potential of the electrode material strongly influences the degree of reaction non-uniformity across the porous electrode, which can be accurately characterized by a dimensionless parameter deduced from the circuit model. The analysis motivates several potential approaches to mitigating localized reaction in phase-changing electrodes. At the particle level, we employ synchrotron-based transmission X-ray microscopy to study the reaction heterogeneity in LiFePO4 secondary particles. Unlike the core-shell reaction geometry often assumed in literature, we observe ubiquitous stripe-like phase pattern on the secondary particle surface, which is independent of the (dis)charging rate and also persists over a wide range of SOC. The experimentally observations are well captured by phase-field simulations, based on which we suggest that the heterogeneous reaction pathway results from the misfit stress induced by the incompatible volume changes between neighbor primary particles of different crystallographic orientations upon lithium insertion / extraction.