Background Methods Although intranasal steroids and anti-cysteinyl-leukotriene-receptor antagonists are efficacious in the treatment of seasonal allergic rhinitis (SAR), combinations of these agents have not unequivocally been demonstrated to be superior to the individual drugs. We aimed to compare the efficacy and potential mechanisms of budesonide nasal spray (BD), oral montelukast (MNT), and combination therapy comprising a half-dose of budesonide plus montelukast (hBD+MNT) in SAR patients. We performed a single-center, randomized, open-label study in SAR subjects (n = 100). Participants were randomized to receive BD (256 mu g), MNT (10 mg), or hBD (128 mu g)+MNT for 14 days. Symptom severity scores, nasal cavity volume (NCV), fraction of exhaled nitric oxide (FeNO), eosinophil cationic protein (ECP), histamine and cysteinyl-leukotrienes (CysLTs), and T-cell subsets were assessed before and after treatment. Results Conclusion All treatments significantly improved symptoms from baseline; however, hBD+MNT produced significantly greater improvements in nasal congestion compared with BD or MNT alone. The BD and hBD+MNT groups had fewer patients with uncontrolled symptoms and improved NCV to a greater level than the MNT group. FeNO was decreased to a significantly greater extent from baseline after hBD+MNT treatment than after BD and MNT treatments. ECP, histamine, and CysLTs showed significantly greater decreases after BD and hBD+MNT treatments than after MNT treatment. BD decreased T-helper 1 (Th1) and Th2 cells and increased T-regulatory (Treg) cells in nasal mucosa and MNT decreased Th1 cells and increased Treg cells in peripheral blood, and this trend was reflected with hBD+MNT. The hBD+MNT combination may have an overall better efficacy profile than BD and MNT monotherapy for treatment of SAR.