Esophageal cancer (EC) is one of the most common cancers in the world, with continuously growing diagnoses and morbidity. Because it is still unclear how to choose the best treatment for EC patients, a multimodal treatment is necessary to improve the prospect of the malignancy, including a sequence of surgery, chemotherapy, and radiotherapy, whether alone or combination. Therefore, this paper aims to analyze the effect of the sequence of chemotherapy, radiotherapy, and surgery on the prognosis and survival rate of patients with EC. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract a dataset of patients who were diagnosed with EC from 1973 to 2015, with follow-up data for 6 years after diagnosis. The data were analyzed using correlation analysis, logistic regression Cox regression, and Kaplan-Meier analysis. EC patients who had radiation prior to surgery and chemotherapy had a better prognosis than the cases without chemotherapy. Based on univariate logistic regression, the odds radios of vital status recoded for "radiation prior to surgery combined with chemotherapy" is the lowest one among the 8 groups classified by radiation sequence with surgery and chemotherapy (P<.001). Further, radiation prior to surgery and chemotherapy is an independent prognostic factor for better survival among EC patients. In conclusion, in the treatment of EC, administering radiation prior to surgery and chemotherapy is better than no radiotherapy, perioperative radiotherapy, postoperative radiotherapy, and other combinations without chemotherapy.