Explosions produced in urban or industrial areas due to accidental or intentional detonation of explosives are low-probability but high-impact events. If standoff distance from buildings or other constructions is small, explosions can cause structural failures and serious injuries or deaths of occupants. Although heavy/stiff enclosure systems were long considered appropriate to protect buildings against explosive threats, lighter and flexible steel-based systems, which are increasingly used for modern buildings, may also provide satisfactory performance. The study presents the results of full-scale blast tests on liner tray walls attached to a steel frame building. Walls were tested against increasing blast charges until failure. Due to very high peak pressures and very short durations, the loading regime could be classified as impulsive. The ultimate strength is given by the failure of the end fasteners, after large bolt hole elongations coupled with the pull-through of the end fasteners. If the insulation and outer cladding are lost, the liner trays are directly exposed to blast and the seaming fasteners at overlapping sheets are prematurely lost. As a result, the wall panels work mostly independently, as one-way elements. On the contrary, if the outer cladding protects the seaming fasteners, the overlapping provides additional capacity due to membrane effect (two-way behavior). Numerical models were calibrated using test data and were further used to obtain more information about liner tray behavior under blast.