Cervical anastomotic leakage (CAL) is one of the most common complications that occur minimally invasive esophagectomy (MIE). It is associated with high postoperative mortality. Some risk factors still remained controversial and so accurate prediction of risk groups for CAL remained very difficult. This study aimed to identify the risk factors of CAL after McKeown MIE to predict the accuracy of the technique as early as possible. A total of 129 patients with esophageal cancer who underwent McKeown MIE at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, between January 2018 and June 2019 were retrospectively reviewed. Multivariate logistic regression analysis was used to identify the risk factors for CAL and receiver operating characteristic (ROC) curve analysis was used to predict the accuracy for each quantitative data variable and determine the cutoff value. There were statistically significant differences between Group CAL and Group NCAL in FEV1 (p = 0.031), neoadjuvant chemotherapy (p = 0.001), intraoperative minimum PaCO2 (p = 0.002), and hospital stays (p <0.001). In multivariate logistic regression, FEV1 (OR = 0.440, p = 0.047), neoadjuvant chemotherapy (OR = 4.425, p = 0.003), and intraoperative minimum PaCO2 (OR = 1.14, p <0.001) were identified to be three risk factors of CAL. The ROC curve analysis showed that FEV1 <2.18L (p = 0.029) and intraoperative minimum PaCO2 >45.5 mmHg (p = 0.002) demonstrated good accuracy. FEV1, neoadjuvant chemotherapy, and intraoperative minimum PaCO2 in arterial blood gas (ABG) were considered as risk factors of CAL after McKeown MIE for esophageal cancer. Preoperative FEV1 <2.18L and intraoperative minimum PaCO2 >45.5 mmHg in ABG showed good accuracy in predicting risk factors for CAL.