We aimed to compare the outcomes and postoperative complications of patients with esophageal cancer after single-port thoracoscopic esophagectomy (SPTE) and four-port thoracoscopic esophagectomy (FPTE). We retrospectively collected data from patients who underwent surgery at the First Affiliated Hospital of Kunming Medical University from February 2019 to November 2022. In total, 86 patients were included in the SPTE group and 114 patients were included in the FPTE group. Compared to patients undergoing FPTE, significantly shorter postoperative hospital stay (13.54 +/- 3.88 vs. 19.08 +/- 5.09 days), shorter chest drainage time (6.06 +/- 2.16 vs. 7.45 +/- 1.68 days), lower estimated intraoperative blood loss (226.05 +/- 94.87 vs. 363.16 +/- 78.92 mL), and longer overall length of surgery (346.34 +/- 53.86 vs. 332.89 +/- 28.86 min) and longer length of abdominal surgery (183.46 +/- 33.33 vs. 166.05 +/- 22.07 min) were observed among patients undergoing SPTE; however, no significant difference was observed regarding 3-month, 6-month, and 12-month overall survival, time to start oral feeding, and length of thoracic surgery. Furthermore, postoperative intractable pain lasting for 3 months (39.5% vs. 21.0%), pneumonia (34.2% vs. 11.6%), empyema (14.9% vs. 3.5%), and chylothorax (10.5% vs. 2.3%) were significantly more frequent in the FPTE group, whereas postoperative gastrointestinal symptoms (41.9% vs. 23.7%) were significantly more frequent in the SPTE group. There was no significant difference between the groups regarding postoperative arrhythmia, recurrent laryngeal nerve injury, esophagotracheal fistula, second surgery, and intractable pain lasting for 6 and 12 months. Compared to FPTE, SPTE may improve patients' outcomes and prevent some of the major complications.