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Purpose The purpose of this analysis is to predict worsening post‐treatment normal tissue toxicity in patients undergoing accelerated partial breast irradiation (APBI) therapy and to quantitatively identify which diagnostic, anatomical, and dosimetric features are contributing to these outcomes. Methods A retrospective study of APBI treatments was performed using 32 features pertaining to various stages of the patient's treatment journey. These features were used to inform and construct a Bayesian network (BN) based on both statistical analysis of feature distributions and relative clinical importance. The target feature for prediction was defined as a measurable worsening of telangiectasia, subcutaneous tissue induration, or fibrosis when compared against the observed baseline. Parameter learning for the network was performed using data from the 299 patients included in the ACCEL trial and predictive performance was measured. Feature importance for the BN was quantified using a novel information‐theoretic approach. Results Cross‐validated performance of the BN for predicting toxicity was consistently higher when compared against conventional machine learning (ML) techniques. The measured BN receiver operating characteristic area under the curve was 0.960±$\,{\pm}\,$0.013 against the best ML result of 0.942±$\,{\pm}\,$0.021 using five‐fold cross‐validation with separate test data across 100 trials. The volume of the clinical target volume, gross target volume, and baseline toxicity measurements were found to have the highest feature importance and mutual dependence with normal tissue toxicity in the network, representing the strongest contribution to patient outcomes. Conclusions The BN outperformed conventional ML techniques in predicting tissue toxicity outcomes and provided deeper insight into which features are contributing to these outcomes.