People with severe mental illness have greater risk of un-detected and inadequately treated medical disorders, adding up to the risk of premature death. This study investigated how chronic medical comorbidity evolved across the lifespan in schizophrenia and the associated impact on mortality. A register-based retrospective nested case-control study was conducted, identifying incident cases of cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), cancer and diabetes, as well as mortality due to these diseases, across the lifespan in schizophrenia. A schizophrenia cohort consisting of 4924 individuals aged 18-40 years registered with a diagnosis of schizophrenia (ICD-8: 295.0-3 + 295.9) during admission to a psychiatric hospital unit in 1970-79. Schizophrenia cases were age and gender matched with 22,597 controls in the general population. Rate ratio (RR) of CVD and cancer were similar to controls. The RR of COPD and diabetes were increased across the lifespan. The probability of having been diagnosed prior to dying from CVD, cancer, pulmonary diseases or diabetes was markedly reduced in schizophrenia cases compared to controls. The RR of all-cause mortality and mortality from CVD, COPD and diabetes remained elevated in all age groups in schizophrenia. Registration of medical comorbidity was associated with increased survival. Excess medical comorbidity persists across the lifespan and into older age. No age-related decrease in incidence of major chronic medical comorbidities in schizophrenia was found except for diabetes.