Background: Neoadjuvant chemoimmunotherapy has been successfully used in resectable non-small cell lung cancer (NSCLC) patients. However, its application in advanced stage unresectable NSCLC remains a topic of debate. This retrospective study was designed to evaluate the efficacy and safety of neoadjuvant chemoimmunotherapy followed by surgical resection in patients with initial unresectable stage III NSCLC, focusing on the surgical resection rate and the survival benefits of surgery. Methods: Patients unresectable stage III NSCLC who received 2-4 cycles of neoadjuvant chemoimmunotherapy between January 2021 and December 2022 were retrospectively identified. Data on characteristics, radiological and pathological responses, and survival outcomes were collected. Results: In total, 148 patients with unresectable stage III NSCLC were recruited. After the last cycle of neoadjuvant therapy, 105 (70.9%) patients were evaluated to be eligible for surgery, and 102 patients ultimately underwent surgery. The rate of complete (R0) resection was 100%, with a major pathological response (MPR) observed in 63.7% and a pathologic complete response (pCR) in 41.2%. Postoperative complications were observed in 9 patients (8.8%), and there was no surgical-related mortality within 30 days. With a median follow-up of 21.9 months, the median progression-free survival (PFS) was 19.6 months in the non-surgery group and not reached in the surgery group. The median overall survival (OS) was not reached in either group. Conclusions: The use of neoadjuvant chemoimmunotherapy is effective in converting unresectable stage III NSCLC into resectable NSCLC. Subsequent radical surgery is safe with low complications and surgical-related mortality.