This paper proposes a second-order sliding mode controller for a three-dimensional overhead crane in an extremely complicated operation with uncertain system parameters. Three actuators composed of trolley-moving, bridge-traveling, and cargo-hoisting forces simultaneously drive fine outputs comprising bridge motion, trolley translation, cable length, and two payload swing angles. Simulation and experiment are performed to investigate the controller qualities. The proposed controller asymptotically stabilizes and consistently maintains system response even when some system parameters are extensively varied.