Introduction: Although cycling is increasingly being promoted for transportation, the safety concern of bicyclists is one of the major impediments to their adoption. A thorough investigation on the contributing factors to fatalities and injuries involving bicyclist. Method: This paper designs an integrated data mining framework to determine the significant factors that contribute to the severity of vehicle-bicycle crashes based on the crash dataset of Victorian, Australia (2013–2018). The framework integrates imbalanced data resampling, learning-based feature extraction with gradient boosting algorithm and marginal effect analysis. The top 10 significant predictors of the severity of vehicle-bicycle crashes are extracted, which gives an area under ROC curve (AUC) value of 0.8236 and computing time as 37.8 s. Results: The findings provide insights for understanding and developing countermeasures or policy initiatives to reduce severe vehicle-bicycle crashes.