Working memory (WM) dysfunction is considered a cardinal feature of schizophrenia. Typically developing adolescents show significant gains in WM performance, which have been attributed to increased “frontalisation” within the fronto-cingulate-parietal network that underpins WM. We used functional magnetic resonance imaging and psycho-physiological interaction to measure blood oxygenation level–dependent signal and functional connectivity in response to the 2-back WM task from 25 youths with EOS and 25 yoked healthy adolescents that were assessed twice with a mean interval of 4 years between assessments. Patients showed reduced prefrontal connectivity at baseline and the magnitude of this effect increased over the follow-up period. Our results suggest on-going functional connectivity abnormalities in EOS patients’ post-disease onset that are linked to prefrontal dysfunction and contribute to worsening WM despite anti–psychotic treatment.