A phenomenological multi-response multi-parameter Acetone–Butanol–Ethanol fermentation dynamic model is developed and calibrated for fermentation process studies. The model was constructed based on other models reported in the literature and was calibrated with a maximum likelihood parameter estimation over Acetone–Butanol–Ethanol fermentation experimental data from the literature. After parameter estimation, a rigorous statistical analysis was conducted to evaluate standard deviations of estimated parameters and predicted responses as well as their respective 95% probability confidence intervals for correct parameters and responses. The significance of parameters was assessed via a Fisher’s F test. From the Base-Model with 17 parameters, a tight, more compact, Reduced-Model was developed with 9 highly significant parameters after deleting 8 nonsignificant parameters from the Base-Model and re-estimating the remaining 9 parameters. This Reduced-Model showed good adherence to the experimental data and had better performance comparatively relative to the Base-Model with 17 parameters using two different inhibition functions reported in the literature. The Reduced-Model is sufficiently good for preliminary engineering and economic assessments of ABE fermentation processes.