Background: Chronic illnesses are increasingly prevalent worldwide and often coexist with psychological disorders such as depression and anxiety, which negatively impact patients’ quality of life, treatment adherence, and clinical outcomes. Despite this burden, data on the prevalence of depression and anxiety among hospitalized chronic illness patients in Bangladesh, especially in tertiary care, remain limited. Objective: This study aimed to determine the prevalence of depression and anxiety among chronic illness patients admitted into medicine department at Al Haramain Hospital, Sylhet and to explore associated demographic and clinical factors. Methods: A hospital-based cross-sectional study was conducted from April 2023 to March 2024 where 302 adult patients were diagnosed with chronic diseases. Depression and anxiety were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Sociodemographic and clinical data were collected through structured interviews and medical records. Data were analyzed using descriptive statistics and logistic regression. Results: Among patients, 38.4% were aged over 60 years, and 53.6% were male. Diabetes Mellitus (35.8%) and Hypertension (31.8%) were the most common chronic illnesses. Most patients (43.0%) had illness duration exceeding five years. Depression was identified in 72.2% of patients, predominantly mild (31.8%) and moderate (24.5%). Anxiety was present in 68.2%, mainly mild (33.8%) and moderate (21.2%). Females had higher rates of depression (76.4%) and anxiety (71.4%) than males. Depression prevalence increased with illness duration, reaching 78.5% among those ill for over five years, and was highest in patients with chronic kidney disease (81%) and diabetes (76.9%). Overall, 47.4% experienced mental health issues; 20.5% had both depression and anxiety. Conclusion: Routine mental health screening and integrated interventions are urgently needed in chronic illness care to improve outcomes and quality of life. Multidisciplinary approaches including mental health professionals are recommended, alongside further multicenter research to develop culturally appropriate interventions in Bangladesh.