Acute type A aortic dissection is a life-threatening condition requiring immediate surgical intervention. However, the optimal arterial cannulation site for cardiopulmonary bypass during surgery remains a subject of debate. Axillary cannulation (AXC) is thought to provide neuroprotective benefits due to antegrade perfusion, whereas femoral cannulation is more accessible but may be associated with increased risk of retrograde embolization and malperfusion. Conflicting findings from observational studies and large registries necessitate a comprehensive evidence synthesis. This systematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and registered with the International Prospective Register of Systematic Reviews, evaluated clinical trials and cohort studies comparing AXC and femoral cannulation in acute type A aortic dissection repair. Databases searched included PubMed, Embase, and Cochrane Library through July 2025. Primary outcomes were in-hospital and operative mortality, with secondary outcomes including stroke, neurological complications, renal failure, and operative parameters. Twenty studies encompassing over 5500 patients were included. AXC was significantly associated with reduced in-hospital mortality [risk ratio (RR) = 0.46], stroke (RR = 0.79), and neurological complications (RR = 0.72). No significant differences were observed in operative mortality, organ malperfusion, re-exploration for bleeding, or renal failure. Sensitivity analyses addressed heterogeneity and reinforced the robustness of effect estimates. Additionally, AXC showed advantages in intensive care unit (ICU) stay and operative metrics, such as cardiopulmonary bypass time and circulatory arrest duration. These findings support AXC as a favorable approach when anatomically and technically feasible, particularly in centers equipped for antegrade cerebral perfusion. However, high-quality randomized controlled trials are required to validate these observations and guide definitive clinical practice.