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Purpose This study aims to investigate survival outcomes and prognostic factors for upward nasopharyngeal carcinoma (NPC) patients receiving radiation therapy (RT) combined with chemotherapy (CT). Methods A total of 421 previously untreated, newly diagnosed T4N0-1 NPC patients, who were identified within the Surveillance, Epidemiology, and End Results (SEER) registry (years 2004–2015), were collected and retrospectively reviewed. All patients received treatment of RT and CT. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The differences in OS and CSS were compared using Log-rank test. The independent prognostic factors were established by using univariate and multivariate Cox proportional hazard models. Results With a median follow-up duration of 37 months (range: 3-154 months), the 5-year estimate OS and CSS rates were 59.3% and 63.7%, respectively. N0 and ≥ 65 years were poor prognostic factors for OS and CSS. Moreover, histology and race were associated with OS and CSS. Univariate analysis indicated that ≥ 65 years, N0, NHB and grade III were unfavorable independent prognosticators of OS and CSS. Multivariate analysis demonstrated that ≥ 65 years, N0 and NHB were correlated with poor OS and CSS. Conclusion Patients with stage T4N0-1 NPC receiving RT plus CT had favorable OS and CSS. Moreover, age, N stage and race were independent prognostic factors of OS and CSS.