Limited research has investigated whether clinicians around the world find diagnostic criteria for depression that were originally developed in the West are useful with diverse populations. Using an embedded mixed-methods design in India, we examined (a) clinicians' and trainees' (n = 143) ratings of the usefulness of the criteria for Major Depressive Disorder (MDD) outlined in two major diagnostic systems (Diagnostic and Statistical Manual of Mental Disorders-5; DSM-5 and International Classification of Mental and Behavioral Disorders-Tenth Edition; ICD-10), and (b) narrative descriptions of clinical cases of adolescent depression and usefulness of diagnostic and screening instruments in day-to-day practice using semi-structured interviews in a subsample of clinicians (n = 24). Qualitative findings demonstrated that Indian clinicians identified markers of depression that were consistent with the current diagnostic manuals (affective, cognitive, somatic symptoms), and the numeric ratings suggested that clinicians found a majority of DSM-5 and ICD-10 criteria for MDD to be useful. However, Indian clinicians also identified additional markers of adolescent depression (i.e., interpersonal conflicts and issues, impairment in school-related functioning, anger-based symptoms, anxiety-based symptoms, additional somatic complaints not included in DSM-5 or ICD-10), highlighting the need to modify existing diagnostic criteria to be more inclusive. The findings suggest the need for culturally informed diagnostic practices that consider a wide range of clinical presentations of depression among adolescents worldwide.