This paper presents the development and characterization of a novel microelectromechanical systems (MEMS) inertial switch that uses a microscale liquid-metal (LM) droplet in a microstructured channel as the active component. Our inertial switch made use of the advantageous properties of the LM droplet (i.e., high surface tension, high density, and electrical conduction) and the microstructured surface. The channel surface was selectively modified to form microstructures that enhanced the non-wetting behavior while minimizing the contact angle hysteresis (CAH) of the LM droplet on the surface. Integrating the LM droplet, which was used as an inertial-proof mass, inside the configured channel containing microstructures on the surface, an inertial switch with a dramatically simplified, yet effective, mechanism was realized. Various channel configurations can be designed for different threshold levels of acceleration.