Cognitive flexibility is a major facet of executive functions and often refers to sequential task control; that is, it is very likely that one may re-encounter a task that has previously been abandoned to carry out a different task. In the context of sequential cognitive flexibility, the “backward inhibition (BI) effect” has been studied quite extensively. Here we ask whether there are age-related differences between adolescents and adults to overcome BI and what system-neurophysiological mechanisms underlie these modulations. This was examined using a system neurophysiological study procedure combining event-related potentials data with source localization and EEG signal decomposition methods. We show that sequential cognitive flexibility, and the ability overcome backward inhibition, is inferior in adolescents compared with adults. Accounting for intra-individual variability in the neurophysiological data, this data suggest that two partly inter-related processes underlie the differences between adolescents than adults to overcome backward inhibition: One process refers to the suppression of the inhibitory effect of the n-1 trial on the n-2 trial during perceptual categorization of incoming information that is associated with right inferior frontal regions. The other process refers to immature response selection and conflict monitoring mechanisms associated with regions in the medial frontal cortex.