<p>Neural interfaces can restore or augment human sensorimotor capabilities by converting high-bandwidth biological signals into control signals for an external device via a decoder algorithm. Leveraging user and decoder adaptation to create co-adaptive interfaces presents opportunities to improve usability and personalize devices. However, we lack principled methods to model and optimize the complex two-learner dynamics that arise in co-adaptive interfaces. Here we present computational methods based on control theory and game theory to analyse and generate predictions for user–decoder co-adaptive outcomes in continuous interactions. We tested these computational methods using an experimental platform in which human participants (<i>N</i> = 14) learn to control a cursor using an adaptive myoelectric interface to track a target on a computer display. Our framework allowed us to characterize user and decoder changes within co-adaptive myoelectric interfaces. Our framework further allowed us to predict how changes in the decoder algorithm impacted co-adaptive interface performance and revealed how interface properties can shape user behaviour. Our findings demonstrate an experimentally validated computational framework that can be used to design user–decoder interactions in closed-loop, co-adaptive neural interfaces. This framework opens future opportunities to optimize co-adaptive neural interfaces to expand the performance and application domains for neural interfaces.</p>