Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential recordings during this task revealed a highly ordered temporal progression of high gamma (HG, 70–200 Hz) activity across the lateral hemisphere in less than 1 sec. The sequence demonstrated concurrent regional sensory processing of speech syllables in the posterior superior temporal gyrus (STG) and speech motor cortex, and then transitioned to sequential task-dependent processing from prefrontal cortex (PFC), to the final motor response in the hand sensorimotor cortex. STG activation was modestly enhanced for target over nontarget sounds, supporting a selective gain mechanism in early sensory processing, whereas PFC was entirely selective to targets, supporting its role in guiding response behavior. These results reveal that target detection is not a single cognitive event, but rather a process of progressive target selectivity that involves large-scale rapid parallel and serial processing in sensory, cognitive, and motor structures to support goal-directed human behavior.