Inhibition and Working Memory (WM) are crucial predictors of everyday life autonomies in people with Down Syndrome (DS). We aimed to investigate the possible relationship between different levels of autonomy, inhibitory sub-components and WM in people with DS. Twenty-two adolescents and adults with DS were enrolled in the study and were assessed with tasks tapping on response inhibition, interference suppression and WM. With a questionnaire on levels of autonomy, educators evaluated the sample with DS. Considering levels of autonomy, we divided participants into two groups: one with lower levels of autonomy and one with medium-to-high levels of autonomy. Results showed differences between the two groups in WM tasks and both inhibitory dimensions. More specifically, interference suppression seems to have a major role in the acquisition of important, more structured aspects of autonomy such as shopping, behaviour on the road, communication and reading-writing skills. On the other hand, response inhibition seems to be linked to crucial aspects of learning, such as reading and writing and handling a telephone. The results are discussed in terms of possible implementation in training in clinical and educational settings.