We developed a complete computer-controlled smart 3-dimensional gas chromatography (3-D GC) system with an automation algorithm. This smart 3-D GC architecture enabled independent optimization of and control over each dimension of separation and allowed for much longer separation time for the second- and third-dimensional columns than the conventional comprehensive 3-D GC could normally achieve. Therefore, it can potentially be employed to construct a novel GC system that exploits the multidimensional separation capability to a greater extent. In this Article, we introduced the smart 3-D GC concept, described its operation, and demonstrated its feasibility by separating 22 vapor analytes.