Background: Many patients with schizophrenia experience psychiatric symptoms long before being diagnosed. We investigated patterns of pre-diagnostic psychopharmacological treatment in individuals diagnosed with first-episode schizophrenia during the last two decades. Design: Using Danish nationwide healthcare registers, we identified all individuals aged ≥10 years registered with their first ICD-10 schizophrenia diagnosis between January 1999 and March 2019. For each calendar year from 1999 to 2019, we calculated the proportion of patients – among those having received their first schizophrenia diagnosis in the respective calendar year – who redeemed prescriptions for various psychotropics in the two years preceding the schizophrenia diagnosis. We calculated proportions of all pre-diagnostic prescriptions since 1995 for a sub-population diagnosed 2011–2019 and for an age- and sex-matched reference group without schizophrenia. Results: Among 33,361 individuals with schizophrenia (58 % males), the schizophrenia incidence rate was stable during the study period but the mean age at diagnosis decreased by >10 years. In the two pre-diagnostic years, 69 % received psychopharmacological treatment (52 % antipsychotics, 40 % antidepressants). This was stable between 1999 and 2019. Among 14,425 individuals diagnosed 2011–2019, psychotropic drug use was observed among 14–20 % between 24 and 10 years before the diagnosis, being four times higher than the reference group. Particularly antipsychotic and antidepressant drug use increased steadily during the ten pre-diagnostic years. Conclusions: Pre-diagnostic psychotropic drug use in schizophrenia was frequent but stable between 1999 and 2019 despite an earlier identification of schizophrenia patients. Our findings emphasize the continued importance of thorough diagnostic interviews, particularly among patients in need of antipsychotic treatment.