Background/Objectives: Understanding the pathogenesis of chronic lymphocytic leukemia (CLL) has led to the development of new prognostic and diagnostic tools, and efforts are underway to extend survival with new prognostic markers and treatment agents. This study aims to evaluate the factors affecting the prognosis and survival of patients with CLL via a retrospective study. Methods: Accordingly, the demographic features of, clinical and laboratory findings for, and hematological parameters and treatment responses of 178 CLL patients who were followed between 1 January 2015 and 31 December 2024 were analyzed before and after treatment protocols were carried out. Results: During the follow-up period, 40.8% of the patients received medical therapy, with 42.5% achieving complete remission, 49.3% experiencing partial remission, and 8.2% demonstrating no response to the treatments. The results demonstrated that an advanced Binet stage, the presence of splenomegaly, a positive direct Coombs test, the presence of a 17p deletion, thrombocytopenia, and elevated creatinine, leukocyte, and lymphocyte counts were associated with increased mortality. Elevated Binet and Rai stages, the existence of 17p deletion, and reduced hemoglobin levels were identified as statistically significant factors. Conclusions: Given the unfavorable prognosis of CLL patients exhibiting a positive direct Coombs test and compromised renal function, further investigations are required to validate the necessity of more rigorous monitoring and, possibly, early intervention. These findings underscore the importance of identifying high-risk factors in CLL to optimize patient management and improve long-term outcomes.