The Stroop effect is a classical, well-known behavioral phenomenon that refers to robust interference between language and color information. It remains unclear when the interference occurs and how it is resolved in the brain. Here we show that the Stroop effect occurs during perception of color–word stimuli and is resolved by a cross-hemispheric, excitatory-inhibitory functional loop involving the lateral prefrontal cortex and cerebellum. Participants performed a Stroop task and a non-verbal-stimulus control task, the Swimmy task, and made a response vocally or manually. The Stroop effect involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of whether the response was made vocally or manually. Such cross-hemispheric lateralization was absent during the Swimmy task. The prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity. This fronto-cerebellar loop may implement language and cognitive systems to achieve a behavioral goal.