Provided are a three-dimensional semiconductor device and a method of operating the same. The three-dimensional semiconductor device includes: a plurality of word line structures on a substrate; active semiconductor patterns between the plurality of word line structures; and information storage elements between the plurality of word line structures and the active semiconductor patterns. Each of the plurality of word line structures includes a plurality of word lines spaced apart from each other and stacked, and the active semiconductor patterns include electrode regions and channel regions, the electrode regions and the channel regions having different conductive types and being alternately arranged.