Background: Sickle cell disease (SCD) is a genetic hematological disorder associated with significant mortality and a range of complex complications that manifest differently across various age groups. Methods: This study aimed to evaluate the demographic, clinical, and laboratory characteristics of SCD patients in Taif City, Saudi Arabia, with a focus on variations among children, adolescents, adults, and middle-aged individuals. A multicenter retrospective cohort study included 129 patients with confirmed diagnosis of SCD between January 2018 to October 2023 and divided into 4 cohorts. The analysis compared hospital stay durations, admission rates, SCD complications, and medication usage. Results: Among the participants, 35 were children (27%), 18 adolescents (14%), 63 adults (49%), and 13 middle-aged individuals (10%). Clinical complications as splenic disease in children (34.3%) were more frequent compared to adolescents (5.6%) and adults (4.8%). Additionally, chronic kidney disease was more prevalent in middle-aged patients (15.4%). Pain was reported in 65.1% of patients, with vascular occlusive crises occurring in 41.1%. Treatment adherence varied, with children showing higher penicillin use (74.3%), while opioid usage was greater in middle-aged patients (76.9%). Conclusions: The findings underscore the necessity for age-specific management strategies in SCD. Further research with larger populations is suggested to enhance the understanding of disease progression and treatment efficacy across different age groups.