A three-dimensional semiconductor memory device including a peripheral circuit structure on a first substrate, the peripheral circuit structure including peripheral circuits, a second substrate on the peripheral circuit structure, an electrode structure on the second substrate, the electrode structure including a plurality of electrodes that are stacked on the second substrate and a penetrating interconnection structure penetrating the electrode structure and the second substrate may be provided. The penetrating interconnection structure may include a lower insulating pattern, a mold pattern structure on the lower insulating pattern, a protection pattern between the lower insulating pattern and the mold pattern structure, and a penetration plug. The penetration plug may penetrate the mold pattern structure and the lower insulating pattern and may be connected to the peripheral circuit structure. The protection pattern may be at a level lower than that of the lowermost one of the electrodes.