Abstract: In urban logistics, drivers are facing a high-intensity work environment. In view of this, the dynamic changes of drivers’ ability to deliver caused by fatigue is considered in delivery processes, and a vehicle routing optimization model is established with the minimization of total delivery time as the objective. A delivery speed function based on fatigue degree is introduced into the model to quantify the change of drivers′ ability to deliver. Then, a modified artificial bee colony algorithm is designed to solve the model integrated with the breadth-first and depth-first search strategies. Finally, the effectiveness of the proposed model and algorithm is verified through standard testing sets and simulation experiments. Experimental results show that considering the impact of driver fatigue is helpful to maintain the balance of drivers′ workload and reduce the degree of driver fatigue. The results of this study may have an important reference significance for delivery planning of logistics enterprises.