Background In 2016, Melbourne was struck by the world’s largest and most devastating epidemic thunderstorm asthma (ETSA) episode. While affected individuals displayed worsened short-term asthma control, little is known about their longer-term natural history, nor about interventions that restore control. Objective We assessed the asthma symptomatology and related behaviours of ETSA-affected individuals through a single-centre prospective 5-year longitudinal study. We embedded an open-label observational trial investigating the role of grass pollen sublingual tablet (Oralair) allergen immunotherapy in improving asthma and allergic rhinitis symptoms. Methods Allergic rhinitis symptom severity, frequency of asthma symptoms and inhaled corticosteroid usage were assessed via questionnaire yearly. In 2018, a subgroup of participants was enrolled in an observational study of Oralair treatment compared to control. The active group received Oralair from 2019 to 2021; both groups were followed-up for 5 years. Subgroup analyses were performed for participants with complete datasets, and who completed the trial per-protocol. Results Year-on-year data across 5 years was available for 30 participants. The rate of persistent asthma symptoms declined from 37% to 7% in 2016 to 2021. Only 10%–27% of participants reported being completely asymptomatic in any given year. The inhaled preventer prescription rate was 67%, with only 35% being adherent. Twenty-seven participants with available data completed the Oralair trial per-protocol. No significant difference was noted between control and active groups for allergic rhinitis symptoms or asthma control, although the Oralair group saw a significant improvement in asthma control comparing 2019 with 2021. Conclusion This is the longest documented follow-up of ETSA-affected individuals. Five years following sentinel event, there was progressive reduction but some persistence in asthma symptoms. Oralair allergen immunotherapy did not further improve allergic rhinitis or asthma symptoms compared to control, but there were no further ETSA events to test a protective effect during the study period.