Laminated glass is used in high-security buildings to mitigate the effects of blasts and ballistic loadings. The multi-layered composition of the laminated glass (LG) panels allows the glass panes to crack and undergo large deflections while preventing glass shards from spalling by mostly remaining attached to the polymeric interlayer. To characterize multilayer LG panels under blast loading, it is essential to develop their static resistance response under uniform loading. A full-scale water chamber was used to experimentally evaluate the quasistatic response to the failure of the multilayer LG panel systems under uniform pressure. The influence of different polymeric interlayer types on the response of multilayer LG panels was studied. Also, the glass breakage patterns and deflections exhibited by various multilayer glass configurations were investigated. The response of LG panels under blast was developed using ANSYS AUTODYN, which was verified using field experiments. LG panels with an Ethylene Vinyl Acetate (EVA) polymeric interlayer experienced the most dynamic deflections, whereas LG panels with an ionoplast SentryGlas® (SG) polymeric interlayer displayed the least dynamic deflections. The results indicated that multilayer LG systems provide higher blast resistance compared to double-layer systems; the additional layers can help reduce glass breakage and maintain structural integrity. Multilayer LG system’s SG interlayer enhanced blast protection by allowing load transfer and ensuring uniform load distribution between glass layers.