Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is the standard first-line treatment for EGFR mutation-positive non-small-cell lung cancer (NSCLC) and demonstrates favorable disease control. Conversely, immune checkpoint inhibitors (ICIs) that target programmed cell death-1/programmed cell death ligands demonstrate a restrictive tumor response. We herein report a patient who achieved a durable response to pembrolizumab following early progression within two months of osimertinib administration for EGFR mutation-positive lung adenocarcinoma. Our findings suggest that treatment with ICIs for patients with EGFR mutation-positive NSCLC experiencing early progression to osimertinib as first-line treatment might represent a viable approach.