β-Blockers are a standard therapy for acute myocardial infarction (AMI) due to their better short-term and long-term outcomes. However, β-blockers are often under-prescribed in chronic obstructive pulmonary disease (COPD) patients with AMI, since they are thought be related to bronchospasm. The aim of this study was to investigate the association between the usage of β-blockers and the risk of mortality in COPD patients after first AMI via a nationwide, population-based cohort study. In this retrospective study, we identified 186,326 patients with AMI diagnosed between January 2000 and December 2012, 23,116 of whom had COPD, from the National Health Insurance Research Database. A total of 7609 patients (32.92%) were prescribed β-blockers, while 15,507 were not. The β-blocker patients were stratified into selective and non-selective β-blocker groups. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Selective β-blocker use showed a reduced risk of mortality, as compared with patients without β-blockers (HR 0.93; 95% CI 0.89–0.98; p < 0.01) while non-selective β-blocker groups did not increase the risk of mortality compared to the patients without β-blockers (HR 0.98; 95% CI 0.94–1.02; p = 0.38). In addition, the use of β-blockers was found to be associated with a reduced risk of mortality in most stratified analyses which was seen particularly in males, patients aged 65 years and above, and in individuals with an array of comorbidities. These findings suggest that β-blockers improve overall survival among COPD patients after first AMI.