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Background: Takotsubo cardiomyopathy (TTC) is a stress-induced condition with limited evidence-based treatment options. Beta-blockers are commonly used, yet their efficacy remains uncertain. This meta-analysis evaluates the impact of beta-blocker therapy on mortality and recurrence in TTC patients. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Semantic Scholar, alongside trial registries and grey literature, for studies from inception to March 2025. Included studies examined adult TTC patients treated with beta-blockers versus controls, reporting all-cause mortality and recurrence. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with I statistics, and publication bias was evaluated via funnel plots. A meta-regression explored ejection fraction (EF) as a moderator of mortality outcomes. Results: Nineteen studies (n=11,167 patients, predominantly female, mean age 59–74 years) were included. Beta-blocker therapy significantly reduced all-cause mortality by 28% (OR 0.72, 95% CI: 0.62–0.84, p=0.00; I=0.30) across 19 studies. Subgroup analyses showed a non-significant 21% reduction in 1-year mortality (OR 0.79, 95% CI: 0.54–1.16, p=0.23; I=0.52) and a significant 29% reduction in 2–5-year mortality (OR 0.71, 95% CI: 0.61–0.82, p=0.00; I=0.07). Recurrence decreased by 29% (OR 0.71, 95% CI: 0.52–0.97, p=0.03; I=0.57), with a mean follow-up of 2.6 years. Meta-regression showed no significant moderation of mortality by EF (p=0.638), suggesting consistent benefits across cardiac function levels. Conclusions: Beta-blockers significantly reduce long-term mortality and recurrence in TTC, with less clear short-term benefits and no variation by EF. These findings support their use in sustained TTC management, though randomized trials are needed to confirm causality and optimize protocols.