Objective: To investigate the effect of clinical pathway-oriented airway management on early rehabilitation in patients with severe traumatic brain injury (sTBI) undergoing tracheotomy. Methods: A total of 146 sTBI patients were randomly divided into observation group (n = 73) and control group (n = 73). The control group received routine nursing care, while the observation group was implemented with clinical pathway-based airway management. All patients were evaluated for outcome indicators, airway humidification and complications after 8 weeks of intervention. Results: After intervention, the observation group had significantly higher airway humidification satisfaction (87.5%, p < 0.05), lower incidence of pulmonary infection (30.0%, p < 0.05) and lower incidence of airway bleeding (27.5%, p < 0.01) than the control group. The sputum aspiration frequency [2 (1,2), p < 0.01], single-patient tracheotomy care time [4 (3,5) min, p < 0.01], and tracheostomy cannula indwelling time (35.80 ± 18.22 d, p < 0.01) in the observation group were significantly lower or shorter than those in the control group. The successful decannulation rate was significantly higher (47.5%, p < 0.05). Conclusion: Clinical pathwaybased airway management can effectively improve sputum characteristics, reduce pulmonary infection and airway bleeding, shorten tracheostomy cannula indwelling time, improve decannulation success rate and promote prognosis in sTBI patients with tracheotomy.