Objectives: The objective of the study was to retrospectively investigate the safety and efficacy of computerized tomography-guided microwave ablation (MWA) in the treatment of Stage I non-small cell lung cancers (NSCLCs). Material and Methods: This retrospective, single-center study evaluated 21 patients (10 males and 11 females; mean age 73.8 ± 8.2 years) with Stage I peripheral NSCLCs treated with MWA between 2010 and 2020. All patients were surveyed for metastatic disease. Clinical success was defined as absence of FDG avidity on follow-up imaging. Tumor growth within 5 mm of the original ablated territory was defined as local recurrence. Welch t -test and Fisher’s exact test were used for univariate analysis. Hazard ratio (HR) and odds ratio (OR) were determined using Cox regression and Firth logistic regression. Significance was P < 0.05. Data are expressed as mean ± standard deviation. Results: Ablated tumors had longest dimension 17.4 ± 5.4 mm and depth 19.7 ± 15.1 mm from the pleural surface. Median follow-up was 20 months (range, 0.6–56 months). Mean overall survival (OS) following lung cancer diagnosis or MWA was 26.2 ± 15.4 months (range, 5–56 months) and 23.7 ± 15.1 months (range, 3–55 months). OS at 1, 2, and 5 years was 67.6%, 61.8%, and 45.7%, respectively. Progression-free survival (PFS) was 19.1 ± 16.2 months (range, 1–55 months). PFS at 1, 2, and 5 years was 44.5%, 32.9%, and 32.9%, respectively. Technical success was 100%, while clinical success was observed in 95.2% (20/21) of patients. One patient had local residual disease following MWA and was treated with chemotherapy. Local control was 90% with recurrence in two patients following ablation. Six patients (28.6%) experienced post-ablation complications, with pneumothorax being the most common event (23.8% of patients). Female gender was associated with 90% reduction in risk of death (HR 0.1, P = 0.014). Tumor longest dimension was associated with a 10% increase in risk of death ( P = 0.197). Several comorbidities were associated with increased hazard. Univariate analysis revealed pre-ablation forced vital capacity trended higher among survivors (84.7 ± 15.2% vs. 73 ± 21.6%, P = 0.093). Adjusted for age and sex, adenocarcinoma, and neuroendocrine histology trended toward improved OS (OR: 0.13, 0.13) and PFS (OR: 0.88, 0.37) compared to squamous cell carcinoma. Conclusion: MWA provides a safe and effective alternative to stereotactic brachytherapy resulting in promising OS and PFS in patients with Stage I peripheral NSCLC. Larger sample sizes are needed to further define the effects of underlying comorbidities and tumor biology.