Background It is unclear whether definitive chemoradiation (CRT) results in improved overall survival compared to radiation therapy (RT) alone in patients with vulvar cancer who are not candidates for surgery. We compared these treatment strategies in the National Cancer Database (NCDB). Methods We identified 1352 patients with pathologically-confirmed squamous cell carcinoma of the vulva treated with definitive RT (n = 353) or definitive CRT (n = 999) between 2003 and 2014 in the NCDB. Exclusion criteria were metastatic disease at diagnosis, RT dose < 4000 cGy, follow-up < 6 months, and surgical treatment. Overall survival was compared using Kaplan-Meier method with log-rank test. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed. Results The median age overall was 66 (23–90) years. The CRT group was younger (p < 0.001) and had more advanced FIGO staging (p < 0.001) compared to the RT group. Median radiation dose was 5940 (4000–7920) cGy. The median follow-up for living patients was longer in the CRT group (45.2 months [6.0–131.6]) than RT (34.4 months [6.1–127.6]) (p = 0.004). The 5-year overall survival was higher in the CRT group compared to RT (49.9% vs. 27.4%, p < 0.001). On multivariate analysis, CRT was associated with a reduced hazard of death compared to RT (HR: 0.76 [0.63–0.91], p = 0.003). The effect remained significant after propensity score matching (HR: 0.78 [0.63–0.97], p = 0.023). On subgroup analysis, patients with FIGO stage I only had a trend towards improved survival with CRT (p = 0.058). Conclusions In the NCDB, definitive chemoradiation was associated with higher overall survival compared to radiation alone in patients with squamous cell carcinoma of the vulva who did not receive surgery. These findings suggest that concurrent chemoradiation may be beneficial for select patients in the definitive setting.