Assessing the potential and extent of earthquake-induced liquefaction is paramount for seismic hazard assessment, for the large ground deformations it causes can result in severe damage to infrastructure and pose a threat to human lives, as evidenced by many contemporary and historical case studies in various tectonic settings. In that regard, numerical modeling of case studies, using state-of-the-art soil constitutive models and numerical frameworks, has proven to be a tailored methodology for liquefaction assessment. Indeed, these simulations allow for the dynamic response of liquefiable soils in terms of effective stresses, large strains, and ground displacements to be captured in a consistent manner with experimental and in-situ observations. Additionally, the impact of soil properties spatial variability in liquefaction response can be assessed, because the system response to waves propagating are naturally incorporated within the model. Considering that, we highlight that the effect of shear-wave velocity V s spatial variability has not been thoroughly assessed. In a case study in Metropolitan Concepcion, Chile, our research addresses the influence of V s spatial variability on the dynamic response to liquefaction. At the study site, the 2010 Maule M w 8.8 megathrust Earthquake triggered liquefaction-induced damage in the form of ground cracking, soil ejecta, and building settlements. Using simulated 2D V s profiles generated from real 1D profiles retrieved with ambient noise methods, along with a PressureDependentMultiYield03 sand constitutive model, we studied the effect of V s spatial variability on pore pressure generation, vertical settlements, and shear and volumetric strains by performing effective stress site response analyses. Our findings indicate that increased V s variability reduces the median settlements and strains for soil units that exhibit liquefaction-like responses. On the other hand, no significant changes in the dynamic response are observed in soil units that exhibit non-liquefaction behavior, implying that the triggering of liquefaction is not influenced by spatial variability in V s . We infer that when liquefaction-like behavior is triggered, an increase of the damping at the shallowest part of the soil domain might be the explanation for the decrease in the amplitude of the strains and settlements as the degree of V s variability increases.