Chronic Obstructive Pulmonary Disease (COPD) exacerbations significantly impact patient morbidity, mortality, and healthcare utilization. Interventions led by nurses are now seen as effective means of improving COPD management and reducing exacerbation related complications. This study aimed to evaluate the impact of nurse-led interventions in the management of COPD exacerbations by a prospective, multicenter, randomized controlled trial. The interventions included comprehensive patient assessments, individualized treatment plans, medication management, oxygen therapy titration, inhaler training, and smoking cessation counseling. The research included 300 COPD patients with exacerbations, with the outcomes assessed in terms of exacerbation frequency, duration, severity, lung function, quality of life, dyspnea severity, and medication adherence. The results revealed that the nurse-led interventions resulted in a significant reduction in exacerbation frequency, duration, and severity as compared to the control group. The intervention group also showed improvements in the lung function, quality of life, dyspnea severity, and medication adherence. Interventions led by a nurse are one of the keyways to enhance COPD exacerbation management and patient outcomes.