Background: Depression is one of the most common psychiatric disorders observed among patients suffering from chronic medical illnesses. The coexistence of depression with chronic diseases such as diabetes, hypertension, chronic kidney disease, and chronic obstructive pulmonary disease can significantly worsen clinical outcomes, reduce treatment adherence, and impair quality of life. Early detection and management of depression in such patients are therefore essential. Aim and Objectives: To determine the prevalence of depression among patients with chronic medical illnesses and to evaluate its association with various demographic and clinical factors. Materials and Methods: This hospital-based observational cross-sectional study was conducted in the Department of Psychiatry, Geetanjali Institute of Medical Sciences, Jaipur, over a period of 6 months. A total of 50 patients with chronic medical illnesses were included in the study. Socio-demographic and clinical data were collected using a structured proforma, and depression was assessed using a standardized depression screening scale. Statistical analysis was performed to determine the association between depression and different variables. Results: The prevalence of depression among patients with chronic medical illness was 42%. Depression was more common among female patients and those with longer duration of illness (≥5 years), showing statistically significant associations. Variables such as age group, socioeconomic status, marital status, and type of chronic illness did not show statistically significant associations with depression. Conclusion: Depression is highly prevalent among patients with chronic medical illnesses and is influenced by several demographic and clinical factors. Routine screening and early psychiatric intervention are essential for improving treatment outcomes and overall quality of life.