Research in adults suggests that higher peripheral inflammation is associated with increased threat-related amygdala activity and reduced cortico-amygdala connectivity. However, there is limited research in adolescents, which is striking given the major developmental changes that occur in cortico-amygdala circuitry during adolescence. In this study, we examine the association between peripheral inflammation and amygdala activity and connectivity to emotional faces in a community sample of adolescents. Participants included 88 adolescents 12 to 15 years old who provided a blood sample and underwent fMRI scanning while completing a face and shape matching task that included fearful, angry, and happy faces. Blood samples were assayed for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α); IL-6 and CRP were combined into a composite due to their high correlation and TNF-α was analyzed separately. Results indicated that higher TNF-α, but not the composite of IL-6 and CRP, was associated with increased amygdala activity to threatening (fearful and angry) faces and to happy faces, relative to shape matching. Whole-brain analyses also identified associations between TNF-α and neural activity to angry and happy faces in regions outside of the amygdala. Psychophysiological interaction analysis indicated that higher TNF-α was associated with reduced bilateral amygdala connectivity to the left cuneus, right cuneus/calcarine fissure/precuneus, and left supramarginal gyrus/inferior parietal gyrus during angry and fearful faces > shapes and higher IL-6/CRP was associated with reduced bilateral amygdala connectivity to the right postcentral gyrus and right precuneus. Results suggest that peripheral inflammation is associated with increased amygdala activity to emotional face stimuli and reduced amygdala connectivity with occipital and parietal regions. These findings enhance our understanding of the association between peripheral inflammation and neural response to emotional faces, which could inform the development of interventions targeting inflammation for adolescents.