To achieve a deeper understanding of patients who developed esophageal cancer (EC) as a second primary malignancy, which may help guide in clinical practice for these patients in the future. In the primary cohort, EC patients with a prior malignancy were identified from the surveillance, epidemiology, and end result 18 database. The 5 most common types of prior cancers were picked out based on the frequency of occurrence. In addition, Kaplan–Meier and log-rank tests were performed to investigate the survival impacts of prior cancers on EC patients. Besides, a competing-risk model was constructed to explore the relationship between EC-treatment and EC-specific mortality. In the secondary cohort, patients with stage I–III (N0M0) EC from 2004 to 2014 were enrolled. After propensity score matching, univariate and multivariate Cox analyses were developed to determine the prognostic factors for EC patients. A total of 1199 EC patients with a prior cancer were identified in the primary cohort. The 5 most common sites of prior cancers were prostate, female breast, bladder, lung and bronchus, and larynx. Kaplan–Meier analyses revealed that EC patients with prior prostate cancer and bladder cancer had the best overall survival (OS), while those with prior cancers of larynx and lung and bronchus had the worst OS. Fine and Gray competing risks analysis indicated that the administration of surgery was closely associated with better EC-specific survival (P < .001). In the secondary cohort, multivariate Cox analyses found that age at diagnosis, race, tumor grade, tumor extent, nodal status and metastasis stage, histology, and the administration of surgery were prognostic factors for OS and cancer-specific survival in EC patients. Besides, the existence of a prior cancer was an independent prognostic factor for cancer-specific survival. EC remains to be the most important cause of death in EC patients with a prior cancer. EC related treatment should be actively adopted in patients with a prior cancer, as they were more likely to die from EC than the prior cancer. EC patients with a prior cancer had comparable OS than those without.