Because of the undesired consequences, particularly seen in deteriorated performance in real-word workspace, continuous efforts have been made to understand time-on-task (TOT) related mental fatigue. However, our understanding of the underlying neural mechanism of TOT is still rudimentary. In this study, EEG signals were recorded from 26 subjects undergoing a 20-min mentally-demanding psychomotor vigilance test. Instead of a mere two-point comparison (i.e., fatigue vs. vigilant), behaviour and EEG data were divided into 4 quartiles for better revealing the progression of TOT effect. We then employed advanced graph theoretical approach to quantify TOT effect in terms of global and local reorganisation of EEG functional connectivity within the lower alpha (8-10 Hz) band. Interestingly, we found a development trend towards disintegrated network topology with the TOT effect, as seen in significantly increased characteristic path length and reduced small-worldness. Moreover, we found TOT-related reduced local property of interconnectivity in left frontal and central areas with an increased local property in right parietal areas. These findings augment our understanding of how the brain reorganises following the accumulation of prolonged task and demonstrate the feasibility of using network metrics as neural biomarkers for mental fatigue assessment.