Background: This study explores the impact of omalizumab and mepolizumab on the dynamic changes in type 2 (T2) markers (blood eosinophils, serum total IgE) and their correlation with clinical outcomes in T2-high severe asthma. Methods: Ninety patients with T2-high severe asthma treated with omalizumab (n=50) or mepolizumab (n=40) were followed prospectively, with asthma control test (ACT) scores, forced expiratory volume in 1 second (FEV1), acute exacerbations (AE), and steroid use assessed at baseline, 6, and 12 months. Changes in T2 markers were analyzed for their correlations with improvements in clinical outcomes. Results: Both treatments significantly improved ACT scores and FEV1 at 6 and 12 months. AE and steroid use also significantly decreased. Blood eosinophil counts significantly reduced in both treatment groups, while total IgE levels increased with omalizumab but showed a non-significant decrease with mepolizumab at 6 and 12 months. Baseline blood eosinophils and total IgE levels demonstrated a significant moderate correlation in both treatment groups (omalizumab: r = 0.31, p = 0.0403; mepolizumab: r = 0.44, p = 0.0182). In the omalizumab group, higher baseline blood eosinophils were associated with greater FEV1 improvement ( r = 0.65, p = 0.001; r = 0.53, p = 0.012), while in the mepolizumab group, total IgE level reductions correlated with improved FEV1( r = -0.77, p = 0.042; r = -0.66, p = 0.02) at 6 and 12 months. Conclusion: Omalizumab and mepolizumab improved clinical outcomes and uniquely influenced T2 marker dynamics in T2-high severe asthma, with baseline blood eosinophils and total IgE level reductions predicting FEV1 improvements, respectively.