Estimating fuel consumption by hybrid diesel buses is challenging due to its diversified operations and driving cycles. In this study, long-term transit bus monitoring data were utilized to empirically compare fuel consumption of diesel and hybrid buses under various driving conditions. Artificial neural network (ANN) based high-fidelity microscopic (1 Hz) and mesoscopic (5–60 min) fuel consumption models were developed for hybrid buses. The microscopic model contained 1 Hz driving, grade, and environment variables. The mesoscopic model aggregated 1 Hz data into 5 to 60-minute traffic pattern factors and predicted average fuel consumption over its duration. The prediction results show mean absolute percentage errors of 1–2% for microscopic models and 5–8% for mesoscopic models. The data were partitioned by different driving speeds, vehicle engine demand, and road grade to investigate their impacts on prediction performance.