A three-dimensional semiconductor memory device includes stacked structures, vertical semiconductor patterns, common source regions, and well pickup regions. The stacked structures are disposed on a semiconductor layer of a first conductivity type. Each stacked structure includes electrodes vertically stacked on each other and is extended in a first direction. The vertical semiconductor patterns penetrate the stacked structures. The common source regions of a second conductivity type are disposed in the semiconductor layer. At least one common source region is disposed between two adjacent stacked structures. The at least one common source region is extended in the first direction. The well pickup regions of the first conductivity type are disposed in the semiconductor layer. At least one well pickup region is adjacent to both ends of at least one stacked structure.