Significant cost benefits through plant simplification can be achieved if a soluble boron-free lithiated primary water chemistry can be demonstrated to be viable for small modular reactor operation. However, the mechanisms of accelerated corrosion behavior of the zirconium alloy clad material under lithiated and boron-free autoclave conditions have yet to be fully identified. Advanced microstructural characterization of selected samples from the testing program, combined with atomistic simulation, have allowed for a significant development in the understanding of the mechanism of lithium-enhanced acceleration under boron-free conditions. Density functional theory has been used to identify the most stable accommodation mechanisms for lithium in tetragonal, monoclinic, and amorphous ZrO2 and its impact upon the defect population at an atomic scale. Atom probe tomography has confirmed that lithium predominantly segregates to oxide grain boundaries under elevated lithium conditions. The combination of modelling and advanced characterization has suggested that lithium-enhanced acceleration is linked to a local grain boundary effect caused by the segregation of lithium that increases the oxygen vacancy concentration within the usually protective barrier layer and leads to accelerated corrosion rates.