Objective To observe the efficacy, adverse reactions and effect on recurrence rate of omalizumab combined with ebastine tablets in the treatment of chronic urticaria. Methods A total of 60 patients with chronic urticaria admitted to the Department of Dermatology, Beijing Anzhen Hospital, Capital Medical University from June 2022 to June 2025 were selected, and they were divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with ebastine tablets alone, and the observation group was treated with omalizumab combined with ebastine tablets. The Urticaria Activity Score over 7 days (UAS7), treatment effect, serum immune-inflammatory indicators, clinical symptoms, adverse reaction rate and recurrence rate were compared between the two groups. Results The UAS7 score of the observation group after treatment was lower than that of the control group (P <0.05). The total effective rate of the observation group (96.67%) was higher than that of the control group (73.33%) (P <0.05). After treatment, the levels of IgE, CRP and IL-4 in the observation group were lower than those in the control group, and the level of IL-2 was higher than that in the control group (P <0.05). The scores of pruritus degree, wheal number and wheal size in the observation group after treatment were lower than those in the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group (P >0.05). The recurrence rate of the observation group was lower than that of the control group (P <0.05). Conclusion The treatment plan of omalizumab combined with ebastine for patients with chronic urticaria can not only improve the clinical treatment effect, but also optimize the serum immune-inflammatory indicators and clinical symptoms. It does not increase the incidence of adverse reactions after medication, the recurrence rate is low, and has high overall application value.