A three-dimensional semiconductor memory device includes a substrate, an electrode structure including electrodes vertically stacked on the substrate and each having a pad portion, electrode separation structures penetrating the electrode structure and apart from each other in a second direction, and contact plugs coupled to the pad portions. The contact plugs comprise first contact plugs and second contact plugs apart in the second direction from the first contact plugs. The electrode separation structures comprise a first electrode separation between the first and second contact plugs. The first contact plugs are apart in the second direction at a first distance from the first electrode separation structure. The second contact plugs are apart in the second direction from the first electrode separation structure at a second distance, different from the first distance.