Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.