Background: For lobectomy in non-small cell lung cancer (NSCLC), whether interrupting the pulmonary vein first (Vein-first) achieves better perioperative and survival outcomes than interrupting the pulmonary artery first (Artery-first) remains controversial. We conducted this meta-analysis to compare outcomes between the two groups to facilitate better surgical decision-making. Methods: Web of Science, EMBASE, Cochrane Library, Ovid MEDLINE, PubMed, ScienceDirect, and Scopus were searched for eligible studies comparing Vein-first and Artery-first procedures. The primary endpoints were survival indicators [overall survival (OS), disease-free survival (DFS), and lung cancer-specific survival (LCSS)]. Secondary endpoints included intraoperative indicators, hospitalization, and follow-up indicators. Results: After screening 2,505 studies, 8 studies involving 1,714 patients (Vein-First group: 881 patients; Artery-first group: 833 patients) were included. The vein-first group achieved better OS [HR (hazard ratio): 1.46, 95% confidence interval (CI): 1.12-1.91, p = 0.005], DFS (HR: 1.60, 95% CI: 1.23-2.08, p < 0.001), and LOSS (HR: 1.64, 95% CI: 1.16-2.31, p = 0.005). The survival rates of OS at 2-5 years, DFS at 1-5 years, and LOSS at 3-5 years were also higher in the Vein-First group. Subgroup analyses suggested that the advantages of survival in the Vein-First group were primarily embodied in the subgroups of squamous cell carcinoma (SCC) and earlier pathological TNM stage (I-II). Operative time, intraoperative blood loss, total complications, and total recurrences were comparable between the two groups. Conclusions: The Vein-first sequence is the suitable choice of vessel interruption sequence during lobectomy for NSCLC with better survival and similar perioperative outcomes, especially for stage I-II SCC.