Three-dimensional semiconductor memory devices are provided. A three-dimensional semiconductor memory device includes a plurality of word line blocks including a plurality of cell strings that are connected in parallel between a bit line and a common source line. Each of the cell strings includes a plurality of memory cell transistors that are stacked on a substrate in a vertical direction, a plurality of ground selection transistors that are connected in series between the plurality of memory cell transistors and the substrate, and a string selection transistor that is between the plurality of memory cell transistors and the bit line. In each of the cell strings, at least one of the plurality of ground selection transistors has a first threshold voltage, and remaining ones of the ground selection transistors have a second threshold voltage different from the first threshold voltage. Related methods of operating three-dimensional semiconductor memory devices are also provided.