Background: Sickle Cell Disease (SCD) is a genetic blood disorder that significantly impacts the health and well-being of affected individuals. Characterized by abnormal hemoglobin, SCD causes red blood cells to adopt a sickle shape, leading to complications such as vaso-occlusive crises, chronic pain, infections, and organ damage. Despite advances in treatment, SCD remains a major public health challenge, particularly in regions with limited healthcare resources. This study evaluates public awareness and knowledge of SCD among the residents of District Ambala, Haryana, to identify gaps and inform targeted educational interventions. Material and Methods: A descriptive cross-sectional survey was conducted between January 2024 and May 2024 in District Ambala, Haryana. The study targeted adults aged 18 and above who had been residents for at least 12 months. A sample size of 400 adults was determined using a 95% confidence level and a 5% margin of error. Data were collected via an online questionnaire distributed through email and social media platforms. The questionnaire included 20 structured questions on SCD awareness and socio-demographic information. Data were analyzed using Epi Info V7 software, and appropriate statistical tests were applied. Results: The study revealed diverse socio-demographic characteristics among participants, with the largest age group being 29-38 years (27.8%), followed by those aged 49 and above (25.8%). Males constituted 55.5% of the sample, and 53.5% were married. The majority were Hindu (70%), employed (53%), and had at least a high school education (87.5%). Knowledge of SCD varied, with 72.5% correctly identifying the disease, but lower awareness of specific aspects such as diagnosis methods (46.3%) and inheritance patterns (43.8%). Overall knowledge scores categorized 22.8% as 'Very Good', 27.3% as 'Good', 29.8% as 'Fair', and 20.3% as 'Poor'. Significant associations were found between knowledge levels and age, gender, marital status, religion, employment, and education. Conclusion: The study highlights significant socio-demographic disparities in SCD knowledge among District Ambala residents. Despite a fair to good overall knowledge level, critical gaps remain, particularly among older adults, females, and those with lower education. Targeted, culturally sensitive educational interventions are essential to address these gaps and improve SCD literacy, early diagnosis, and disease management. Leveraging digital platforms for broad outreach can enhance public health efforts and ultimately improve health outcomes for individuals with SCD.