Using the Wilhelmy plate technique, the role of chemical defects in hysteretic wetting behavior was investigated. The wetting and dewetting work differ significantly, depending on the defect energy (i.e., high or low energy with respect to the matrix). For one, or an array of high-energy defects, advancing measurements departed from equilibrium theory, while the receding data were in close agreement. Conversely for low-energy defects, only the receding measurements showed significant departure from theory. We propose that distinct wetting mechanisms for high- and low-energy defects explain the phenomenon of asymmetric hysteresis, where the advancing or receding contact angle deviates more strongly from the equilibrium angle.