A three-dimensional semiconductor memory device is disclosed. The device may include a substrate including a cell array region and a connection region provided at an end portion of the cell array region, an electrode structure extending from the cell array region to the connection region, the electrode structure including electrodes sequentially stacked on the substrate, an upper insulating layer provided on the electrode structure, a first horizontal insulating layer provided in the upper insulating layer and extending along the electrodes, and first contact plugs provided on the connection region to penetrate the upper insulating layer and the first horizontal insulating layer. The first horizontal insulating layer may include a material having a better etch-resistive property than the upper insulating layer.