Trait self-control (TSC), defined as the capacity to alter predominant response to promote desirable long-term goals, has been found to facilitate emotional well-being (EWB). However, the neural correlates underlying this association remain unclear. The present study estimated resting-state brain activity and connectivity with amplitude of low-frequency fluctuations (ALFF) and functional connectivity (rsFC) among late adolescents. Whole-brain correlation analysis showed that higher TSC was associated with increased ALFF in regions within the executive control network (inferior frontal gyrus, IFG) and the salience network (anterior insula, AI) and decreased ALFF in regions (e.g., medial frontal gyrus, MFG; posterior cingulate, PC) within the default-mode network (DMN). TSC was also linked with the integration (e.g., increased IFG-PC connectivity) and segregation (e.g., decreased AI-MFG connectivity) among brain networks. Mediation analysis indicated that TSC totally mediated the links from the IFG and the precuneus, FC of the AI and regions of the DMN (e.g., bilateral PC, MFG), to EWB. Additionally, ALFF in the IFG and the MFG could predict negative affect in the pandemic through TSC. These findings suggest that TSC is involved in several regions and functional organizations within and between brain networks and mediated the association between neural correlates and emotional wellness in adolescence.