Unique stimuli stand out. Despite an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, a neural source of salience remains elusive. In an attempt to identify a source of visual salience, we reversibly inactivated parietal cortex and simultaneously recorded salience signals in prefrontal cortex. Inactivation of parietal cortex not only caused pronounced and selective reductions of salience signals in prefrontal cortex but also diminished the influence of salience on visually guided behavior. These observations demonstrate a causal role of parietal cortex in regulating salience signals within the brain and in controlling salience-driven behavior.