Video-assisted thoracoscopic surgery (VATS) has emerged as a less invasive technique for treating resected lung cancer compared with open surgery. In recent years, the uniportal VATS technique has gained popularity for lung resection in small nodules and ground glass lesions. However, it remains unclear whether single-port VATS offers more favorable perioperative outcomes than multi-port approaches. This study aims to evaluate the perioperative outcomes of single-port versus 2-port and 3-port VATS in patients with early-stage non-small cell lung cancer. A literature search was conducted across 5 online databases (PubMed, CENTRAL, ProQuest, SAGE, and ScienceDirect). Meta-analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Study quality was assessed using the risk of bias tool in randomized trials (RoB 2) and the Newcastle-Ottawa Scale, while meta-analysis was conducted with Review Manager (RevMan) 5.4. This study was registered in PROSPERO under protocol number CRD42025634395. A comprehensive initial search identified 9,178 records, of which 22 studies were included in the systematic review and 19 were incorporated into the meta-analysis, with a total of 3,324 participants. Compared with 3-port VATS, single-port VATS was associated with significantly lower intra-operative blood loss (mean difference [MD], -10.52; 95% confidence interval [CI], -17.37 to -3.66; p=0.003), shorter chest tube duration (MD, -0.71; 95% CI, -1.07 to -0.35; p<0.001), lower postoperative drainage volume (MD, -68.25; 95% CI, -117.64 to -18.87; p=0.007), shorter postoperative hospital stay (MD, -1.00; 95% CI, -1.65 to -0.35; p=0.003), and lower pain scores on postoperative day 1 and day 3 (MD, -0.73; 95% CI, -1.19 to -0.28; p=0.002; MD, -0.59; 95% CI, -0.85 to -0.32; p<0.001), as well as a reduced rate of postoperative complications (MD, 0.83; 95% CI, 0.69 to 0.99; p=0.04). No significant differences were observed between single-port and 2-port or 3-port VATS regarding operation time and number of dissected lymph nodes. The risk of bias was low, and the overall certainty was moderate. Single-port VATS is safe and feasible, with short-term outcomes comparable to those of 2-port and 3-port approaches.