Parkinson’s disease leads to a spectrum of cardinal motor symptoms and locomotor deficits that vary in severity with the nature of daily activities and the fluctuating physiology of patients. Many of these deficits remain inadequately addressed by existing therapies that use continuous, activity-agnostic parameters. Instead, adaptive therapies embedding activity-specific parameters have the potential to better address the entire range of symptoms. Here, we expose physiological principles that enable real-time decoding of ongoing locomotor activities across motor fluctuations from the neural dynamics of the subthalamic nucleus. This decoding steered activity-dependent adaptations of deep brain stimulation therapies that improved both cardinal motor symptoms and locomotor deficits across activities of daily living. Our decoding framework provides a blueprint for next-generation neuromodulation therapies that continuously adapt parameters to the behavioral context and fluctuating physiology of each patient. One Sentence Summary Neural decoders that leverage the physiological principles of activity-dependent encoding in the subthalamic nucleus support the implementation of adaptive deep brain stimulation therapies that alleviate locomotor deficits in people with Parkinson’s disease.