Several studies have suggested an association between anemia and asthma, but evidence for causality is limited. Thus, this study investigated the causal relationship between hemoglobin levels and asthma using bidirectional two-sample Mendelian randomization (MR) with summary statistics from large genome-wide association studies (GWAS) of European ancestry. Genome-wide significant genetic variants for hemoglobin levels and asthma were selected as instrumental variables. The inverse variance weighted (IVW) method was employed as the primary MR approach, supplemented by weighted median, MR-Egger, simple mode, and weighted mode. Horizontal pleiotropy was assessed with MR-Egger regression and the MR-PRESSO test, and heterogeneity was tested with Cochran’s Q from MR-Egger and IVW. In the IVW analysis, each genetically predicted 1 g/dL decrease in hemoglobin level was associated with higher asthma risk (odds ratio [OR] 1.162; 95% CI 1.078–1.256). Although some horizontal pleiotropy and heterogeneity were detected, the estimates remained significant in pleiotropy-robust models (weighted median: OR 1.163, 95% CI 1.034–1.309, MR-Egger: OR 1.220, 95% CI 1.048–1.416). No significant causal effects of asthma on hemoglobin levels were observed in any MR approach. These findings support a causal link between lower hemoglobin levels and increased asthma risk. This may help understand of anemia-asthma relationship, suggesting a potential role of hemoglobin levels in asthma pathogenesis.