The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.