The age of onset of schizophrenia is related to variability in cognitive function and clinical characters, and negative symptoms and cognitive function share similar features that could be closely connected. Alterations in brain-derived neurotrophic factor (BDNF) expression and the Val66Met (rs6562) polymorphism are involved in the pathogenesis of the disease, but few studies have explored its influence on the associations of age of onset, cognitive function and clinical symptoms in schizophrenia. The clinical symptoms of a total of 573 patients with chronic schizophrenia were assessed by using the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The serum BDNF level and Val66Met polymorphism were measured after the assessment. Our results showed the following: (1) patients with an earlier age of onset exhibited more negative symptoms and cognitive deficits, as well as lower levels of serum BDNF; (2) negative symptoms and cognitive function showed negative and positive correlations with age of onset, respectively, and worse cognitive function was associated with a high level of negative symptoms and a low level of serum BDNF; and (3) the moderated mediation analyses indicated that negative symptoms partially mediated the relationship between age of onset and cognitive deficits, which was moderated by serum BDNF. The mediating effect of negative symptoms exhibited a Met allele dose-dependent tendency. These results indicate that age of onset, cognitive function, and clinical symptoms of schizophrenia exhibit different relationships under different serum BDNF levels and BDNF Val66met polymorphisms.