Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to study some of the effects of microgravity on human physiology, cognition, and sensorimotor functions. Previous studies have reported declines in balance control and functional mobility after spaceflight and HDBR. In this study we investigated how the brain activation for foot movement changed with HDBR. Eighteen healthy men participated in the current HDBR study. They were in a 6° head-down tilt position continuously for 70 days. Functional MRI scans were acquired to estimate brain activation for foot movement before, during, and after HDBR. Another 11 healthy men who did not undergo HDBR participated as control subjects and were scanned at four time points. In the HDBR subjects, the cerebellum, fusiform gyrus, hippocampus, and middle occipital gyrus exhibited HDBR-related increases in activation for foot tapping, whereas no HDBR-associated activation decreases were found. For the control subjects, activation for foot tapping decreased across sessions in a couple of cerebellar regions, whereas no activation increase with session was found. Furthermore, we observed that less HDBR-related decline in functional mobility and balance control was associated with greater pre-to-post HDBR increases in brain activation for foot movement in several cerebral and cerebellar regions. Our results suggest that more neural control is needed for foot movement as a result of HDBR. NEW & NOTEWORTHY Long-duration head-down bed rest serves as a spaceflight analog research environment. We show that brain activity in the cerebellum and visual areas during foot movement increases from pre- to post-bed rest and then shows subsequent recovery. Greater increases were seen for individuals who exhibited less decline in functional mobility and balance control, suggestive of adaptive changes in neural control with long-duration bed rest.