Background: Walking abnormalities in people with Parkinson’s disease (PD) are characterized by a shift in locomotor control from healthy automaticity to compensatory, executive control, mainly located in the prefrontal cortex (PFC). Although PFC activity during walking increases in people with PD, the time course of PFC activity during walking and its relationship to clinical or gait characteristics is unknown. Objective: To identify the time course of PFC activity during walking in people with PD. To investigate whether clinical or gait variables would explain the PFC activity changes. Methods: Thirty-eight people with PD tested OFF medication wore a portable, functional near-infrared spectroscopy (fNIRS) system to record relative PFC activity while walking. Wearable inertial sensors recorded spatiotemporal gait characteristics. Based on the PFC activity (fNIRS) in the late phase of the walking task (final 40 seconds), compared to the early phase (initial 40 seconds), participants were separated into 2 groups: reduced or sustained PFC activity. Results: People with PD who reduced PFC activity during walking had less impaired gait (eg, faster gait speed) than those who had a sustained increase in PFC activity ( P textless .05). Cognitive set-shifting ability explained 18% of the PFC activation in the group with a sustained increase in PFC activity ( P = .033). Conclusions: The time course of reduction in PFC activity corresponds to less impaired gait performance in people with PD, while a sustained increase in PFC activity is related to worse cognitive flexibility. Reduction in PFC activity while walking may indicate a less impaired, automatic control of walking.